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If you or a loved one is navigating a blood cancer diagnosis, understanding how ROR1-targeted therapies work—and whether they could apply to your specific cancer type—can help you make more informed treatment decisions.

Main points:

ROR1 is a receptor found on the surface of cancer cells, rarely present in healthy adult cells, making it a promising treatment target for various blood cancers.
Early studies show that therapies targeting ROR1—such as CAR T-cell therapy, monoclonal antibodies, and small molecule inhibitors—may be effective in certain blood cancers like CLL and MCL.
Combining ROR1-targeted therapies with other treatments like venetoclax may help overcome drug resistance and improve patient outcomes.

In the sections below, continue reading to learn how these therapies are being tested, which blood cancers they may benefit most, and what early research is revealing about their potential to improve outcomes.

What Is ROR1 and Why Does It Matter for Blood Cancer Patients?

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a protein that plays a role in early development. In adults, it's mostly inactive—but in several cancers, including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), ROR1 is turned back on and helps cancer cells grow and survive.

Because healthy adult tissues show little to no ROR1 activity, therapies that target it are less likely to harm normal cells. This makes ROR1 an appealing focus for developing more precise cancer treatments with fewer side effects.

For other blood cancers like multiple myeloma, acute myeloid leukemia (AML), and large B-cell lymphoma (LBCL), researchers have found ROR1-positive cancer cells in some patients. Early lab studies suggest that targeting ROR1 might help, but more research is needed to know how well these treatments work in real-life settings.

Clinical Trial Treatment Options That Target ROR1

Several types of therapies are being developed to block ROR1 and stop its cancer-supporting activity:

Monoclonal antibodies like cirmtuzumab designed to attach to ROR1 on cancer cells and block its signals. Early trials show this approach may be effective when combined with other treatments like venetoclax, which targets another cancer-promoting protein, BCL-2.
Small molecule inhibitors such as KAN0441571C are designed to enter cancer cells and shut down ROR1 from the inside. These are showing potential, especially in patients whose cancers resist standard therapies.
Antibody-drug conjugates (ADCs) like zilovertamab vedotin deliver chemotherapy directly to ROR1-positive cells, limiting damage to healthy cells. Click here to access a recruiting clinical trial for relapsed/refractory CLL, MCL, and follicular lymphoma patients.
CAR T-cell therapy that modifies a patient’s own immune cells to target ROR1-positive cancer cells. This approach is still in early testing.
Bispecific antibodies engineered to bring T-cells into close contact with cancer cells that express ROR1, helping the immune system do its job more effectively.

Why Combination Therapies Could Be the Future

One of the biggest challenges in blood cancer treatment is drug resistance—when cancer stops responding to treatment. Studies suggest that using a combination of therapies that target different pathways can reduce the risk of resistance.

For example, combining anti-ROR1 therapies with venetoclax may work better than either alone. This is especially important for people with high-risk or relapsed disease.

Bottom Line

If you’re living with CLL, MCL, or another ROR1-positive blood cancer, the development of ROR1-targeted therapies could eventually offer more effective and less toxic treatment options. While many of these therapies are still in clinical trials, early results are promising and could lead to new standard-of-care treatments in the future.

As research continues, it’s important to stay informed about clinical trials and emerging therapies. Talk to your doctor about whether any new treatment options may be appropriate for your specific situation.

Continue Exploring Advancements in Blood Cancer Treatments

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Source:

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Therapeutic advances in the targeting of ROR1 in hematological cancers
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Loncastuximab’s Use for Follicular Lymphoma

Follicular lymphoma that becomes resistant to or comes back after treatment, known as relapsed/refractory, presents significant challenges. A promising approach involves a therapy initially approved for diffuse large B-cell lymphoma (DLBCL), now under investigation for follicular lymphoma.

This treatment is the antibody-drug conjugate loncastuximab tesirine (Zynlonta, ADC Therapeutics). Administered via intravenous infusion, loncastuximab targets the CD19 surface protein on cancer cells and delivers chemotherapy directly to them.

Juan Pablo Alderuccio, MD, from Sylvester Comprehensive Cancer Center, led a study on loncastuximab for relapsed/refractory follicular lymphoma, advancing from a promising phase 1 to phase 2. Phase 2 results were highlighted at the 2024 ASH conference, exploring the benefits of combining loncastuximab with rituximab.

Watch Dr. Alderuccio's interview below, and read on to discover more about the trial's outcomes and eligibility to join.

How Effective is Loncastuximab with Rituximab for Follicular Lymphoma?

The study focused on a group of 39 individuals with relapsed/refractory follicular lymphoma. The average age of the participants was 68, with the majority diagnosed with advanced-stage, high-risk follicular lymphoma. On average, these patients had received one prior treatment regimen, most commonly R-CHOP.

Regarding the effects of combining loncastuximab with rituximab, the outcomes are notable. Twelve weeks after beginning the therapy, 97.4% of the evaluable patients experienced a reduction in cancer cells, 66.7% of which were full reductions as confirmed by PET/CT scans, indicating a complete metabolic response (CMR). For patients who did not achieve a CMR by week 12, treatment continued until week 21. By week 21, the percentage of patients who achieved a CMR increased to 80%.

At the 12-month follow-up since starting treatment, 94.6% of the participants were alive and didn’t show any advancement of the cancer. Most side effects reported were mild, including high blood sugar levels, elevated liver enzymes, fatigue, and rash.

Conclusion and Future Outlook

Dr. Alderuccio's study demonstrated that loncastuximab with rituximab effectively treats individuals with relapsed/refractory high-risk follicular lymphoma. Most patients achieved a complete reduction in cancer cells, experienced mild side effects, and the treatment controlled cancer progression for at least 12 months.

We are eagerly awaiting the results of the combination with a larger group of patients followed for a longer period of time. Click here to check if you are eligible to participate in this study and receive loncastuximab.

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Continue Reading on the Latest Advancements in Follicular Lymphoma Treatment

Does BR or R-CHOP Better Extend the Time to Next Treatment for Follicular Lymphoma?

The researchers evaluated the data of over 2,000 follicular lymphoma patients who had received either BR or R-CHOP as their first treatment. The majority of these patients had advanced-stage cancer at the time of their diagnosis.

The researchers’ main goal was to find which group had a longer period of time without needing the next treatment, referred to as “time to next treatment”.

They found that follicular lymphoma patients treated with BR had a longer time to their next treatment than those who were treated with R-CHOP. The average amount of time for each group was:

8 years for patients treated with BR
6.5 years for patients treated with R-CHOP

Additional Insights from the Study

Other findings gained from the study included:

Overall survival: Patients treated with BR had slightly better overall survival outcomes than patients treated with R-CHOP, meaning they lived for a longer amount of time.
Rituximab maintenance: Continuing therapy with rituximab after the first treatment was associated with better outcomes in terms of the amount of time to the next treatment and overall survival.
Transformation rates: The chance of the cancer transforming into a more aggressive form like DLBCL was slightly higher in patients treated with R-CHOP, especially for those with grade 3A follicular lymphoma.
Use of stem cell transplant: In cases where the cancer advanced quickly after patients’ first treatment, the use of autologous stem cell transplant (ASCT) was similar between the two treatment groups.

Summary

For patients with follicular lymphoma needing their first treatment, the study conducted by Dr. Margaret Kelsey Baron and her team at Huntsman Cancer Institute suggests that BR (bendamustine plus rituximab) might be a more effective option than R-CHOP. It was found that BR extended the time to the next treatment more significantly, offering patients about 8 years before needing further treatment, compared to 6.5 years with R-CHOP. Additionally, BR showed a slight improvement in overall survival rates and was associated with lower transformation rates into more aggressive cancer forms.

If you are considering one of these treatment combinations for your follicular lymphoma treatment, we invite you to talk to your specialist about what would be right for your personal case.

Subscribe to the Follicular Lymphoma Newsletter

Stay updated on follicular lymphoma news with HealthTree. Subscribe to our newsletter today!

Follicular Lymphoma Newsletter

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Real-World Outcomes in Patients with Follicular Lymphoma Treated with R-CHOP vs BR

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Chimeric Antigen Receptor (CAR) T-cell therapy uses a patient’s own immune cells (T-cells) and modifies them in a lab so they are better at finding and eliminating cancer cells. CAR T-cells are engineered to carry a receptor that binds to a specific protein on cancer cells, like CD19, a protein commonly found in certain blood cancers.

CAR T-cell Therapy is Continuously Being Improved

CAR T-cell is groundbreaking for treating cancer because it uses modified healthy immune cells to eliminate cancer cells. Although its use has good responses, the downside is that side effects like cytokine release syndrome, nervous system side effects, and depletion of CAR-T cells (running out of cells), demand further treatment advancements to create improved CAR T-cells that bind only to cancer cells and last longer in the body, minimizing as much as possible the side effects.

Thanks to research, there is more than one CAR-T cell option, depending on what they were designed to do and the proteins they link to. That’s why CAR T-cell therapy is currently one of the most active areas in research, always looking for improvement.

New Clinical Trial Testing Armored CAR T-Cells

A new Phase I clinical trial is now recruiting patients to test a genetically engineered type of CAR T-cell therapy, known as EGFRt/19-28z/IL-12 CAR T-cells, for people with blood cancers that express CD19 and whose cancer came back after treatment (relapsed) or didn’t respond to other therapies (refractory).

What are Armored CAR T-cells?

These armored CAR T-cells target the CD19 protein found on lymphoma cells, and they also have a protein called interleukin-2 (IL-2), which works as an immune system booster (cytokine). Combined, they improve the immune system against cancer and enhance the T-cells' ability to survive and function for longer.

What is the Purpose of the Trial?

The trial seeks to determine the safety, side effects, and best dose of the armored CAR T-cells. The investigators want to find out if, when adding the gene for IL-12, the modified T-cells may fight cancer cells more effectively and improve the overall immune response.

Who Can Join the Trial?

The trial NCT06343376 includes people who previously received CAR T-cell therapy targeting CD19 but need further treatment. This trial includes patients with the following blood cancers that are CD19 positive:

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Diffuse large B-cell lymphoma (DLBCL)
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High-grade B-cell lymphoma (HGBL)
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Chronic lymphocytic leukemia (CLL)
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Mantle cell lymphoma
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Follicular lymphoma
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Visit the trial page for more information on eligibility criteria.

What is the Clinical Trial Plan?

All the patients who participate in this trial will first undergo a procedure called leukapheresis, where their T-cells are collected. Then, depending on the group they are assigned to, they will receive either:

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EGFRt/19-28z/IL-12 armored CAR T-cells alone, or
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A combination of chemotherapy (cyclophosphamide and fludarabine) followed by the armored CAR T-cells.
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Throughout the trial, various tests will monitor the participants’ health and will consist of heart ultrasound, imaging (PET or CT scans), and bone marrow biopsies, to observe their response to the treatment.

After treatment, patients will be closely monitored for side effects and signs of cancer reappearance, with follow-ups occurring over several months and up to 5 years or for as long as each patient agrees to, to assess long-term safety and effectiveness.

Why is This Clinical Trial Important?

This trial represents an exciting new step in CAR T-cell therapy, potentially offering a more effective treatment option for blood cancer patients. By enhancing T-cell function through the addition of IL-12, researchers hope to improve outcomes for patients who have limited options left. If you want to learn more or participate in this trial, it is important to discuss the risks and benefits with your healthcare provider.

If you’re interested in looking for more clinical trials, access HealthTree’s Clinical Trial Finder for free!

Sources:

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Follicular lymphoma is a type of slow-growing non-Hodgkin lymphoma (NHL). It occurs when abnormal white blood cells (lymphocytes) build up in lymph nodes, forming masses or lumps. While the exact cause is often unknown, most people with follicular lymphoma live for many years.

What is Bendamustine?

Bendamustine is a type of chemotherapy medication used to treat various types of cancer, including follicular lymphoma. It was first approved in the US in 2008, and it belongs to a group of drugs called alkylating agents. These drugs work by damaging the DNA of cancer cells, preventing them from multiplying.

Your medical team might also refer to bendamustine by its commercial names: Bendeka or Treanda.

How Does Bendamustine Work?

Bendamustine is administered through a vein (intravenously) and takes about 30-60 minutes to complete. The frequency of treatment depends on the specific cancer and treatment plan.

Like other chemotherapy drugs, bendamustine can cause side effects. These may include:

Increased risk of infection: Due to a decrease in white blood cells
Bleeding or bruising: Caused by a reduction in platelets
Nausea and vomiting: Anti-nausea medications can help
Fatigue: Feeling tired
Digestive issues: Such as sore throat, stomach upset, or rectal discomfort
Headaches: Over-the-counter pain relievers may help

It's important to discuss potential side effects with your doctor and report any concerns promptly.

Bendamustine and Follicular Lymphoma

Bendamustine, often used in combination with rituximab (a type of immunotherapy), can be an effective treatment for follicular lymphoma. Some studies suggest it may be better tolerated than other standard chemotherapeutic regimens like R-CHOP.

However, it's essential to note that every patient is unique. What works for one person may not work for another. Your doctor will carefully consider your individual situation when recommending a treatment plan.

What's New in Bendamustine Research?

Exciting developments in cancer research are exploring new combinations of bendamustine with other novel therapies. Clinical trials are investigating how bendamustine might work even better when paired with other newer medications. These studies aim to find more effective and tolerable treatment options for patients with follicular lymphoma.

For example, a phase I/II trial is investigating the combination of tazemetostat (Tazverik, IPSEN) with bendamustine in patients diagnosed with follicular lymphoma. This study aims to determine the safety and effectiveness of this combination. Explore other clinical trials recruiting patients with follicular lymphoma with Healthtree's Clinical Trial Finder.

Important Safety Considerations

While bendamustine can be an effective treatment option, it's also associated with certain risks. Recent research highlights the importance of close monitoring for infections, especially in patients receiving long-term treatment with rituximab.

Conclusion

Bendamustine is a chemotherapy medication used to treat follicular lymphoma. While it can be an effective treatment option, it's essential to weigh the potential benefits against the risks. As with any cancer treatment, open communication with your healthcare provider is crucial.

The journey through a cancer diagnosis can be overwhelming. Staying informed about treatment options and advancements is essential. Consider joining our newsletter to receive the latest updates on follicular lymphoma and other related topics.

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Sources:

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A non-chemo treatment combination of zanubrutinib (Brukinsa) and obinutuzumab (Gazyva) evaluated in the ROSEWOOD study showed promising results for helping many follicular lymphoma patients whose disease had come back after remission or the cancer cells had stopped responding to treatment achieve a reduction of cancer signs and symptoms. Read more about the study’s findings below.

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What are Zanubrutinib and Obinutuzumab?

\n\n

Zanubrutinib is a non-chemo targeted therapy administered orally that helps kill follicular lymphoma cells. It works by blocking a molecule (Bruton’s tyrosine kinase [BTK]) on the surface of the cancer cell which plays a role in telling the cell to stay alive and keep making new cells. By blocking the BTK receptor, the cancerous B-cell dies. Zanubrutinib is currently available for the treatment of follicular lymphoma patients in clinical trials.

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Obinutuzumab is a type of medicine called a monoclonal anti-CD20 antibody. It is administered by infusion and binds to protein CD20 on the surface of B-cells. Binding to the CD20 protein helps kill the follicular lymphoma cells. Obinutuzumab is currently FDA-approved for the treatment of follicular lymphoma.

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The ROSEWOOD Study

\n\n

The ROSEWOOD study investigated whether adding zanubrutinib in combination with obinutuzumab could create a more effective treatment outcome for relapsed and refractory follicular lymphoma patients compared to treating the cancer with obinutuzumab alone.

\n\n

217 relapsed/refractory follicular lymphoma patients from 17 different countries were split 2 to 1 into the treatment groups. Two-thirds of the patients received zanubrutinib with obinutuzumab. The remaining one-third received obinutuzumab by itself. The therapies were administered over the course of two years.

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Treatment outcomes

\n\n

Zanubrutinib and obinutuzumab group: \n\t
- After 20 months of treatment, 69% of the patients achieved a reduction of cancer signs and symptoms (39% complete reduction, 30% partial reduction)
- Cancer cells did not progress for an average of 28 months from the start of treatment
\n\t
Obinutuzumab group:\n\t
- After 20 months of treatment, 46% of the patients achieved a reduction of cancer signs and symptoms (19% complete reduction, 27% partial reduction)
- At an average of 10.4 months from the start of therapy, the cancer cells stopped responding to treatment and began progressing again. Patients needed to switch to a different line of therapy at an average of 12.2 months from the start of treatment to manage the cancer
\n\t

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Manageable Side Effects

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The most common side effects of the zanubrutinib and obinutuzumab combination included low platelet count (thrombocytopenia), pneumonia, and diarrhea. Patients worked with their healthcare team to help reduce these side effects.

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Key Takeaways

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The findings of the ROSEWOOD study offer promising treatment results of a new non-chemo targeted therapy combination for relapsed and refractory follicular lymphoma patients. We are grateful for the doctors and patients who participate in cancer research to help accelerate cures and improve the quality of life for those living with blood cancer.

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Want to help accelerate a cure for follicular lymphoma? Get involved in research to support the next best treatment options for patients!

\n\n

Join HealthTree Cure Hub Today!

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If you are a newly diagnosed patient with follicular lymphoma, how effective is the bispecific antibody mosunetuzumab (Lunsumio, Genentech) when used as a first treatment for a fixed period of time?

This immunotherapy is currently FDA-approved for follicular lymphoma patients who have had at least two prior treatments, usually including chemotherapy for those with high-tumor burden.

What about moving mosunetuzumab to a front-line instead of a third-line treatment for people with high-burden follicular lymphoma? Bypassing chemotherapy could help reduce the negative side effects patients experience.

Lorenzo Falchi, MD, of Memorial Sloan Kettering Cancer Center, investigated this question in phase 2 of the Mithic-FL1 trial and presented his findings at the 2024 ASH conference.

Watch Dr. Falchi’s interview or read the study’s highlights below to learn how this important trial is paving the way to providing patients earlier access to immunotherapies and moving standard follicular lymphoma treatments away from chemotherapy.

First-Line, Fixed-Duration Mosunetuzumab in the Mithic-FL1 Trial

How Was Mosunetuzumab Administered?

In the study, mosunetuzumab was administered as a subcutaneous injection over the course of 8 cycles (about 6 months; each cycle was 21 days). If patients reached a complete response by that time, meaning cancer cells were not detected by testing, they would stop treatment. However, those who had only achieved a partial response (cancer cells were partially reduced) by the 8-cycle mark, continued to receive the treatment for up to 17 cycles (about 12 months).

Usually, mosunetuzumab is administered by intravenous infusion (IV). The newly developed injection form is an attractive and convenient option for patients who don’t want to wait for an IV. Another benefit of mosunetuzumab is that patients receive it in an outpatient setting, meaning they do not have to stay in the hospital overnight. This provides patients with the flexibility they need to travel to the clinic for their treatment and then go home.

A note about step-up dosing and pre-treatments to expect: To help reduce the risk of patients experiencing side effects, mosunetuzumab was administered by step-up dosing during the first cycle. This strategy slowly and safely increases the medication until it reaches its normal dose.

Another strategy to reduce the risk of side effects in cycle 1 was for patients to receive pre-treatments of an antihistamine (diphenhydramine), a corticosteroid to reduce inflammation (dexamethasone), and acetaminophen.

What Were the Results of the Mithic-FL1 Study?

Overall Response and Complete Response

In the Mithic-FL1 trial, 76 patients with high-burden follicular lymphoma received mosentuzumab treatment. The results were highly promising. The best overall response rate, indicating a partial or complete reduction of cancer cells, reached 95%. Remarkably, 80% of patients achieved a complete response, meaning their cancer was not detected by scans.

Most patients reached a complete response within the first four treatment cycles. However, 9 patients had not achieved complete response by the 8th cycle and continued treatment up to cycle 17. Of these, 4 patients eventually achieved a complete response, either by the 17th cycle or shortly thereafter. Those who still had a partial response after cycle 17 either underwent involved-site radiation to target remaining cancer cells or were closely monitored.

Long-Term Outcomes: Progression-Free Survival and Overall Survival

One year after starting treatment, the long-term outcomes remained very positive:

88% of the patients maintained progression-free survival, meaning they were alive without the cancer progressing
The overall survival rate was 99%, with the vast majority of patients alive at this point

What Were the Side Effects of Mosunetuzumab?

The most common side effects were mild versions of injection site reactions, cytokine release syndrome, infections, muscle/joint pain, dry skin, and fatigue. Only two patients needed to be hospitalized and treated with tocilizumab (an anti-inflammatory therapy) for severe cases of cytokine release syndrome, both of whom recovered. Remarkably, no patients experienced neurotoxicity, a brain-related side effect that causes symptoms like confusion.

Key Takeaways

The results of the Mithic-FL1 trial are very promising for people with high-burden follicular lymphoma. It shows that using the bispecific antibody mosunetuzumab as their first treatment for a set amount of time offers high odds of achieving a complete response that, for the majority of patients, lasted beyond 1 year. The therapy also has manageable side effects and can be administered in an outpatient setting as an injection, making this off-the-shelf antibody an attractive alternative to chemotherapy.

With its promising results, Dr. Falchi’s team hopes that mosunetuzumab will undergo further trials in larger groups and potentially establish a new standard of care for follicular lymphoma treatment.

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Single-Agent Mosunetuzumab Produces High Complete Response Rates in Patients with Newly Diagnosed Follicular Lymphoma: Primary Analysis of the Mithic-FL1 Trial

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People with low-tumor burden follicular lymphoma are usually recommended to observe the cancer without treatment (watch-and-wait/active observation) or be treated with a monoclonal antibody called rituximab. It's unclear when exactly patients should start rituximab.

Once follicular lymphoma advances into high-tumor burden, it is recommended to begin chemotherapy.

Can treating low-burden follicular lymphoma with rituximab early on reduce the risk of it advancing into high-burden disease? If so, it would help patients reduce their risk of needing chemotherapy later on.

Noriko Fukuhara, MD, PhD, from Tohoku University in Japan, and colleagues reviewed in phase 3 of the Flora study whether it was better to give rituximab to untreated patients with low-burden follicular lymphoma or for patients to remain in watch-and-wait.

Dr. Fukuhara presented the findings at the 2024 ASH conference. Read the study’s results below and watch HealthTree’s interview with Dr. Fukuhara.

Is It Beneficial for People with Low-Burden Follicular Lymphoma to Start Rituximab Early? Dr. Fukuhara Says Yes

Phase 3 of the Flora study compared the outcomes of 292 low-tumor burden follicular lymphoma patients from 54 hospitals across Japan. The first group started rituximab immediately, and the second group, in watch-and-wait, waited for the cancer to progress before starting treatment.

The main goal was to see which group had better event-free survival (EFS). EFS measures the length of time after primary treatment that a patient remains free of certain complications or events such as disease progression, need for new treatment, or death.

Results

The study had to be stopped early because results showed that those who started rituximab right away did significantly better than those who waited.
The chance of the cancer not worsening was higher in the rituximab group compared to the watch-and-wait group.
Both groups had similar survival rates, meaning the immediate use of rituximab mainly helped in controlling the cancer rather than prolonging life.

Summary

The Flora study found that starting rituximab treatment early for low-tumor burden follicular lymphoma reduces the risk of the cancer progressing to high-tumor burden. This also decreases the chance of patients needing high-burden treatments like chemotherapy.

Dr. Fukuhara advises patients with low-tumor burden follicular lymphoma to start rituximab therapy right away instead of remaining in watch-and-wait. Talk with your follicular lymphoma specialist if you have questions about treatment.

Glofitamab, a New Immunotherapy For Follicular Lymphoma

More clinical trials and treatment options are being developed to achieve better responses and longer periods of remission. Recently, immunotherapies have emerged as promising options for follicular lymphoma. They help the immune system find and destroy cancer cells while having fewer side effects.

Glofitamab (Columvi) is a new bispecific antibody administered intravenously designed to attach to T-cells that eliminate lymphoma cells, helping relapsed or refractory follicular lymphoma patients. Its unique structure binds to two CD20 molecules on lymphoma cells and one CD3 molecule on T-cells, enhancing the immune response against lymphoma cells. It is currently approved for diffuse large B-cell lymphoma and large B-cell lymphoma derived from follicular lymphoma. It is currently featured in several clinical trials seeking its use for more non-Hodgkin lymphoma types including follicular lymphoma.

Glofitamab in Follicular Lymphoma: Clinical Trial Highlights

Initial results for relapsed/refractory B-cell non-Hodgkin lymphoma

This trial included a total of 171 patients, 44 of them with follicular lymphoma, who were treated with glofitamab following a single dose of obinutuzumab. Initial results showed a 70.5% overall response rate (ORR), including 47.7% of patients who achieved a complete response (CR). The most common side effects were cytokine release syndrome (CRS), fever, and neutropenia. This study is still ongoing and testing other innovative combinations with glofitamab - Check out the participating centers and see if it could be a good fit for you with our Clinical Trial Finder.

Glofitamab in Combination with Polatuzumab Vedotin

A phase II study evaluated glofitamab monotherapy in patients with relapsed or refractory lymphoma who had received at least two prior treatments. Among 154 treated patients, the complete response (CR) rate was 40%, and the overall response rate (ORR) was 52%. After a median follow-up of 37.7 months, the median duration of CR was 29.8 months, with 57% of CR patients remaining progression-free and 77% alive two years after treatment. Biomarker analysis showed a rapid and sustained decrease in circulating tumor DNA (ctDNA) levels in responders, and immune system recovery, including B-cell and immunoglobulin restoration, began around 18 months post-treatment. The safety profile remained consistent with previous findings, with no new severe cytokine release syndrome or fatal adverse events. These results highlight the long-lasting remission potential and immune recovery benefits of fixed-duration glofitamab.

Glofitamab with Englumafusp Alfa trial NCT04077723

Glofitamab is also being studied in combination with englumafusp alfa, an agent that targets CD19 and the receptor 4-1BB on T-cells. This combination showed promising results in a phase 1 trial, with an ORR of 91% and a CR rate of 73% in patients with relapsed/refractory follicular lymphoma.

Glofitamab in combination with bispecific antibody RO7443904 trial

This trial tested the combination of glofitamab with a bispecific antibody that targets CD19 and repels CD28 named RO7443904, to enhance T-cell activity and potentially increase treatment efficacy for aggressive lymphomas.

Combination of Glofitamab with CELMoDs

Combining Glofitamab with CELMoDs is a phase 1 trial still recruiting. CELMoDs are small molecule agents designed to enhance immune activity and improve anti-cancer cells.

Final Thoughts

Glofitamab represents an exciting advancement for relapsed and refractory follicular lymphoma patients, offering more options for those who have tried multiple treatments. Its ability to engage T-cells to target and destroy cancerous B-cells has shown optimistic results in clinical trials, with high response and complete remission rates when combined with other therapies. As research continues, glofitamab and similar bispecific antibodies have the potential to extend remission periods and improve the quality of life for patients while reducing the side effects often seen with conventional treatments.

Keep learning more clinical trial updates with the HealthTree News site!

Here, you can find all articles from different categories, from clinical trials, conferences, patient stories and more!

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If follicular lymphoma comes back after prior treatments (relapsed/refractory), finding therapies that are effective and long-lasting can be a challenge.

Read about the updates on a promising treatment combination that uses epcoritamab, rituximab, and lenalidomide.

Dr. Lorenzo Falchi's Updates from the EPCORE NHL-2 Trial

Lorenzo Falchi, MD, from Memorial Sloan Kettering Cancer Center, explained in an interview with HealthTree at the 2024 ASH conference the results of the EPCORE NHL-2 trial. This study combined a two-year combination of epcoritamab, rituximab, and lenalidomide for relapsed/refractory and high-risk patients with follicular lymphoma.

Watch Dr. Falchi’s interview or read the summary of the research he led below.

How Effective is Epcoritamab + Rituximab + Lenalidomide for Follicular Lymphoma?

Epcoritamab (Epkinly, Genmab and AbbVie) is an FDA-approved third-line bispecific antibody for people with follicular lymphoma. Rituximab (Rituxan, Genentech) and lenalidomide (Revlimid, BMS) are a common follicular lymphoma treatment combination.

To improve outcomes for relapsed/refractory and high-risk patients, Dr. Falchi and colleagues combined these therapies together in the EPCORE NHL-2 trial.

111 people with relapsed/refractory follicular lymphoma received the treatment combination for up to two years.

Epcoritamab was given as a subcutaneous injection (shot under the skin) more frequently during the first three months, then once a month for the second year.
Rituximab was given intravenously (IV) for the first six months.
Lenalidomide was taken as a pill for the first year.

Study Outcomes

Encouraging responses:\n
- 96% of patients responded to the therapy, meaning their tumors shrank.
- 87% achieved a complete response, meaning no signs of follicular lymphoma were found on scans.
- 88% of patients achieved MRD negativity (minimal residual disease testing, a highly precise method of screening remaining cancer cells in a blood sample that, if negative, confirms a deep response achieved).
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Long-lasting benefits:\n
- After nearly two years, 80% of patients remained in remission.
- 90% of patients were alive without significant cancer progression or need for further treatment.
- Even in cases where the lymphoma recurred, many patients didn’t need immediate treatment, as the recurrence was minimal.
\n
Side effects:\n
- The most common side effect that 62% of patients experienced (32% of cases being severe) was neutropenia, causing symptoms like frequent infections and fever. Neutropenia is a known side effect of lenalidomide with rituximab. To reduce its impact in the trial, investigators will shorten the amount of time patients receive epcoritamab during phase 3. Patients can also expect to receive supportive care to help neutrophil counts recover.
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What Do the Study’s Results Mean for People with Follicular Lymphoma?

The results from the EPCORE NHL-2 trial are promising because they show that the combination of epcoritamab, rituximab, and lenalidomide is highly effective. Most patients in the study experienced deep, long-lasting responses to treatment, improving their quality of life.

Specialists are further reviewing this treatment combination in phase 3 of the EPCORE FL-1 trial. Dr. Falchi hopes that with additional testing, this regimen could become the new standard of care for people with relapsed/refractory follicular lymphoma. If phase 3 results prove to be positive, they could support the approval of this combination’s use outside clinical trials.

Messages Others May Be Telling You

After the initial shock of a diagnosis fades, many people with chronic blood cancer face ongoing frustration—especially when they hear, “But you don’t look sick.” Because the cancer isn’t immediately life-threatening or visible, those around them may downplay its seriousness, expecting life to continue as usual.

In The Myth of Normal, Dr. Gabor Maté notes that trauma impacts everyone differently. What may seem minor to onlookers can be something that has a major internal impact on the person experiencing it. This is especially true for people living with chronic blood cancer.

Many of the struggles are invisible: persistent fatigue, increased infection risk, anxiety associated with the uncertainty of cancer progression, and the financial stress of long-term care. Over time, these challenges can become overwhelming. And even when loved ones mean well, not feeling understood or validated can add to the emotional toll.

In her new book, The Big C ² - stories from the chronic side of cancer, Ruth Fein writes about Michele, who lives with chronic leukemia.

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Recently, two of her closest friends made comments that had Michele trying desperately to keep her raised eyebrows from freezing in place. “You are lucky you have never really felt bad,” is the paraphrase she remembers. “What?!?”
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“Well, we always thought you looked great, so you must feel great,” they said when she finally had a heart-to-heart with them about how shocked she was by their comments.
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“These were days that I couldn’t even fathom picking up the phone; I didn’t even want to get dressed or wash my hair... or get out of bed,” she recalls thinking. Then she was hit by the common denominator. She never explained, even to her besties, how badly she was feeling.
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Messages You May Be Telling Yourself

You might feel you need to push yourself to meet the expectations of others or based on how you want others to see you. While it can be difficult to feel your cancer is minimized by friends or family, you also don’t want to be treated as a cancer “victim” who is always needy. There is a natural desire to hold on to the life and identity you had before your diagnosis. Not fully accepting and sharing your new or changing reality is one way your mind may try to protect you.

One of the most helpful things you can do is find ways to focus on the parts of yourself that bring you joy and purpose while acknowledging the reality of your health and any related limitations.

For example, if you’re naturally social but feel isolated due to infection risks, talk to your doctor about preventative strategies that could help you safely reconnect with others.

Openly sharing your values, routines, and goals with your doctor can also help shape a care plan that better supports your day-to-day emotional well-being. And if you don’t feel truly heard by your care team, it might be time to look at other more supportive options.

You’ll find a list of specialists by blood cancer type at the end of this article. A trusted healthcare provider can make all the difference, along with a team that includes a social worker, mental health professional, or others who can help you integrate your physical and emotional health needs.

Setting You Up for Success

Building healthy coping strategies and surrounding yourself with supportive people who understand what you're going through is essential—especially when you are triggered by comments like, “You don’t look sick,” while you are struggling internally.

Finding support groups that include other patients with similar experiences may help validate your feelings. If you find it difficult to process your experiences or communicate your needs to others, working with a licensed therapist—either one-on-one or with family—can be incredibly helpful.

If you feel pressured by those around you to act as if nothing has changed since your diagnosis, symptoms, and treatments, it’s important to set clear boundaries. Let them know what support actually looks like for you. You can be both direct and kind. When loved ones are aware of strategies to help you feel more seen, understood, and empowered, they are more able to help you feel your best.

Below, we’ve included examples of responses you can say if someone says, “But you don’t look sick.”

Responding to “You Don’t Look Sick”

1. Acknowledge the good intent, but clarify the impact:

“I appreciate that, and I know you mean well, but comments like that can actually make me feel like a “cancer imposter” – like I’m not really going through this.”
“Thanks, I know it might seem like I’m okay on the outside, but it doesn’t reflect how I feel inside.”

2. Use “I” statements to express how it feels:

“I know I don’t look sick, and that’s actually one of the hardest parts—because I’m really struggling internally.”
“I’ve learned that appearances can be deceiving, even to myself sometimes.”

3. Gently educate if the moment feels right:

“It’s an invisible illness—things like fatigue, brain fog, and pain don’t always show up physically.”

4. Share more if they seem open; if not, protect your energy:

“If you’re curious, I’d be happy to share what it’s really like to live with this.”
Or simply: “Thanks,” and move on if that’s more comfortable at the time.

5. Validate your own experience:

You don’t have to justify how you look to others or yourself. While it poses emotional challenges not to look sick, it can also help you feel better about yourself, even while you don’t feel well on the inside.
When it comes to lengthy explanations, save your energy for people who truly matter—those who want to understand.

Bottom line: Use direct communication, not defensiveness. Assume good intent, but honor your truth. You can advocate for understanding without having to prove your pain.

Summary

Living with an invisible illness like chronic blood cancer comes with unique emotional and social challenges, but you don’t have to face them alone. By embracing your reality, setting healthy boundaries, and seeking support that validates you, you can reclaim a sense of control and connection.

Connect with a Chronic Blood Cancer Specialist

If you haven’t already, it’s important to connect with a specialist who focuses on your type of chronic blood cancer. They can offer the best care to improve both your quality and length of life, whether that involves active monitoring, access to the best FDA-approved treatments or clinical trials, or support for managing side effects.

To find a specialist, click the directory link below that matches your type of chronic blood cancer:

Chronic eosinophilic leukemia (CEL)
Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL)
Chronic myeloid leukemia (CML)
Chronic myelomonocytic leukemia (CMML)
Chronic neutrophilic leukemia (CNL)
Essential thrombocythemia
Follicular lymphoma
Multiple myeloma
Myelodysplastic syndromes (MDS)
Myelofibrosis
Polycythemia vera
Waldenstrom's macroglobulinemia

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Responding to “You Don’t Look Sick”

1. Acknowledge the good intent, but clarify the impact:

2. Use “I” statements to express how it feels:

3. Gently educate if the moment feels right:

4. Share more if they seem open; if not, protect your energy:

5. Validate your own experience:

Summary

Connect with a Chronic Blood Cancer Specialist