Insights From Treatment Patterns and Outcomes in Plasma Cell Leukemia (PCL)

Plasma Cell Leukemia (PCL) is considered as an extremely rare, aggressive variant of Ultra High-Risk Multiple Myeloma (UHRiMM) with less than two hundred annual newly diagnosed patients in the US and with a short survival  duration despite the use of novel therapies.

A recent paper published in Haematologica states that PCL remains an understudied disease for which there is no current standard of care. Knowledge on new emerging therapies, including the role and timing of hematopoietic stem cell transplant as primary and salvage therapy is needed. 

There are two variants of PCL:

• Primary plasma cell leukemia (pPCL) arises de novo, meaning it is diagnosed for the first time as a new occurrence. This subtype presents more severe symptoms and genetic abnormalities.
• Secondary plasma cell leukemia (sPCL) develops from multiple myeloma (MM).

What Do Recent PCL Studies Tell Us?

Unlike the wealth of information that is available for the newly diagnosed multiple myeloma patients, there is little literature available for the newly diagnosed PCL patient (regardless of the diagnosis of pPCL or sPCL). There are, however, two recent retrospective studies available that MAY be of some use. There are NO prospective studies available.

The study from Haematologica is the largest multi-center analysis from patients diagnosed with pPCL and sPCL. Between January 2010 and January 2021, data was collected from electronic medical records at seven academic centers in the United States.

Another study, published in the journal Blood covers pPCL (NO sPCL) treatments and outcomes from 3 US academic centers.

By comparing the two studies, you can obtain some guidance on which therapeutic approach is best for each case, and then discuss it with your healthcare team. 

There are a number of observations that can be made. Please note that the reported outcomes are specific to newly diagnosed PCL patients, and the outcomes presented in the Blood paper are only applicable to pPCL patients.

Comparing Treatment Patterns and Survival

The following trends emerged:

• Transplantation improves survival:

  • Median overall survival (OS) for patients who received any transplant was 48.7 months, compared to 5.9 months for those who did not.

  • For pPCL patients: 49.5 vs. 12.5 months.

  • For sPCL patients: 16 vs. 3.4 months.

  • Allogeneic (donor) transplants did not show better outcomes than autologous (self) transplants.

• Younger patients were more likely to receive transplants.

• Depth of response (MRD negativity) was greater in transplant recipients, suggesting longer-term disease control.

Key takeaway: Transplantation continues to offer the best survival advantage for eligible patients. And further research shows that it can significantly decrease risk of relapse by 88% and the risk of  death by 69%. 

The goal of using induction therapy for people with a PCL diagnosis is to decrease the amount of the cancer as fast as possible. There are two main treatment modalities that have been use:

• VTD-PACE (bortezomib-thalidomide-dexamethasone-cisplatin-doxorubicin-cyclophosphamide-etoposide) requires a hospital stay of around one week.It seems to be used more often in sPCL.
• VRd (Velcade-Revlimid-dexamethasone) can be done on an outpatient basis requires anywhere from 4 to 8 three-week cycles of treatment. This therapy is more often used in pPCL.

Your MM/PCL specialist will make the decision as to what will be best for you. On a personal note: I have heard from fellow pPCL patients that, more recently, sometimes Daratumumab is added to VRd triplet. 

Which Type of Transplantation is Best?

There has been a debate over the past 10 years in the pPCL community as to what is the best transplant option: single auto SCT, tandem auto-auto SCT, or tandem auto-allo SCT. 

Over time, there seems to be more of a consensus that, for those patients who are transplant eligible, the auto-auto tandem transplant option seems to have the best outcomes. The Blood paper indicates a median overall survival of 75 months. On a personal note, 75 months median OS for newly diagnosed pPCL patients is mind-blowing considering that about 10 years ago the median survival for pPCL was about 11 months.

What’s Next for PCL Research?

Future investigations should focus on improving the response rates, particularly in sPCL. New therapies such as BCL-2 inhibitor venetoclax, have shown potential in inducing responses in pPCL cases with t(11;14), a translocation more commonly observed in this subtype.

Improved responses with venetoclax have also been noted in relapsed sPCL cases harboring t(11;14) FISH abnormalities. Additionally, bispecific T-cell engagers targeting B-cell maturation antigen (BCMA), CD-19, and other targets represent promising avenues for future investigation. While the results of CAR-T therapy in PCL have been modest, continued research in this area is warranted. The integration of MRD-directed maintenance approaches may help determine the minimum treatment durations necessary to achieve optimal survival. In other words, it is too early to tell.

Paul Kleutghen's Insights

I would like to recommend that for those patients who are in the early stages of their PCL journey, they read the Heamatologica paper thoroughly as there are other interesting points that I did not summarize in this post.

I wish I had this paper handy when I started my own pPCL journey nearly 12 years ago. I did have the good fortune, though, that my specialist had just returned from the European hematology meeting where the Italian myeloma consortium presented compelling data about moving forward with auto-auto tandem less than a week before I was supposed to start the “allo” portion of my auto-allo tandem. However, please be reminded that every MM or PCL patient is unique from our fellow patients, and we need to listen closely to our specialist and ask numerous questions to determine the best course of action for you.

Any new or recently diagnosed pPCL patients are most welcome to contact me directly through HealthTree and I will do my very best to answer your questions. 

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