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Side Effect Solutions for CLL Treatments

CLL patients can use the below tips to help reduce side effects that may appear when taking targeted therapies for the treatment of CLL. If patients have further questions, they should reach out to their CLL specialist

Venetoclax (venclexta)   

Venetoclax is a non-chemo targeted therapy. It targets CLL cells by blocking the BCL-2 protein which regulates cell survival and death. It is taken via tablets by mouth often in combination with an antibody treatment (administered by IV) for a fixed period of time (12 or 24 months for 1st or 2nd line therapy). It typically helps reduce CLL cells to a state of remission (reduction of signs/symptoms of CLL), however, CLL typically resurfaces between 2-5 years after treatment. If signs of CLL progress to the point of lymph nodes are enlarged, spleen and/or liver are enlarged, or red blood cell and/or platelet counts are low, the patient would come out of watch and wait to need treatment again to manage the CLL. See here for more information about venetoclax. 

Venetoclax Side Effects and Tips to Reduce Them 

  • Tumor lysis syndrome (TLS) 
    • Drink 6-8 glasses of water each day starting two days before and on the day of the first dose and each time the dose increases
    • Patients can receive IV fluids from their doctor while they ramp up on the medicine to reduce TLS
  • Diarrhea 
    • Pepto Bismol 
    • Imodium
    • Fiber 
  • Nausea
    • IV fluids
    • Anti-nausea medication like Zofran (ondansetron)
    • Ginger 
  • Neutropenia
    • Neupogen injection
  • Infections (UTI, upper respiratory infection, etc)
    • Monitor immunoglobulin (IGG) levels. If low, administer an IV of immunoglobulin 
    • Antibiotic - Long-term low dose of bactrim (trimethoprim-sulfamethoxazole) until treatment period over
  • Fluid buildup in the body
    • Cold compress on the area for a few minutes 
    • Elevate the swollen area above heart level 
    • Limit sodium in diet
    • Exercise
    • Diuretics 
  • Muscle aches/pains (resolved when fixed treatment is over) 
    • Low-dose prednisone (anti-inflammatory) 
    • Hot water and Epsom salts 

BTK Inhibitors 

BTK inhibitors are non-chemo targeted therapies that block the bruton’s tyrosine kinase (BTK) protein in the BCR pathway causing CLL cells to die (may also affect normal B-cells). They are administered by oral tablets long-term. They typically help reduce CLL cells to levels of remission. Taking BTKis over time, however, can cause the CLL cells to mutate and become resistant to the treatment. If this happens patients will need to switch to other types of CLL treatments like venetoclax. 

  • Types of BTKis - ibrutinib (1st approved BTKi has more side effects than second generation BTKis), zanubrutinib and acalabrutinib (recently approved BTKis have less side effects than ibrutinib)
  • If a CLL patient has been taking a BTKi for a few years and has side effects, they should consult their CLL specialist to see if they can take a break from taking the BTKi to see if their side effects improve

BTKi Side Effects and Tips to Reduce Them 

  • More common
    • Infections (from weakened immune system/suppresses immunity because BTKis impact CLL cells [mutated B-cells] and some normal B-cells which are in charge of making antibodies to fight infections)
      •  Monitor immunoglobulin (IGG) levels. If low and patient has frequent infections, administer an IV of immunoglobulin 
      • Antibiotic - Long-term low dose of bactrim (trimethoprim/sulfamethoxazole)
    • Fatigue - caused by CLL cells dying off. It make take a few weeks to months to resolve 
    • Lymphocyte count increasing then decreasing (normal as CLL cells move from the lymph nodes into the bloodstream to die)
    • Diarrhea
      • Pepto Bismol 
      • Imodium
      • Fiber 
    • Bruising (from blood thinning caused by BTKis) 
      • Typically resolves on its own. If it doesn’t, consult with your CLL specialist who may advise you to pause taking the BTKi for 2-3 days while the bruise heals 
    • Brittle nails 
      • Biotin supplement 
      • Moisturizing gloves with Aquaphor
      • See a dermatologist
    • Neutropenia
      • Injection of Neupogen 
    • Headaches (for first few weeks starting BTKi then passes)
      • Small amounts of caffeine
      • Tylenol 
  • Less common side effects 
    • Joint pain/muscle cramps while body adapts to BTKi 
      • Switch to a different type of BTKi
      • Low-dose prednisone (anti-inflammatory) 
    • Rash
      • If mild:
        • Over-the-counter antihistamine like Benadryl
        •  Topical hydrocortisone cream
    • Atrial fibrillation
      • Switch to a different CLL treatment like venetoclax that doesn’t cause blood thinning 
    • Raised blood pressure (consult with CLL specialist to review which of the following is needed)
      • First try angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor-blockers (ARB)
      • If the above doesn't work, try either carvedilol, spironolactone, hydralazine, or oral nitrates
      • If the patient is intolerant to beta-blockers, use verapamil and diltiazem
      • Switch to other CLL treatments like venetoclax
    • Increased bleeding
    • Neuropathy 
      • If non-painful type of neuropathy, reduce BTKi dose 
      • If painful type of neuropathy, use gabapentin to manage pain
      • Change to different CLL medicine like venetoclax 
    • Mouth sores (mucositis) inflammation of the mucous membranes 
      • Reduce BTKi dose 

CAR T-cell Therapy

CAR T-cell therapy enhances the patient’s cancer-killing T-cells to destroy CLL cells. For some CLL patients, it has cured their cancer. CAR T-cell therapy is currently approved for other types of blood cancers however is in clinical trials to get approved for CLL treatment. To learn about CAR T-cell therapy and join recruiting clinical trials to get CAR T approved, see here

After the CAR T infusion, patients are monitored at the facility for a week to provide solutions to possible side effects. Most patients fully recover from CAR T-cell therapy side effects. 

Tips to decrease CAR T-cell therapy side effects

  • Nausea 
    • IV fluids
    • Anti-nausea medication like Zofran (ondansetron)
    • Ginger 
  • Cytokine release syndrome (CRS)
    • Tocilizumab injection 
    • Corticosteroids
  • Neurological (Mild: Headaches, Serious: Confusion, difficulty finding words, Severe and rare: Coma)
    • Corticosteroids 
  • Infections 
    • Antibiotics 
    • Prophylactic antimicrobials

Need further help managing CLL treatment side effects? Reach out to a CLL specialist. HealthTree also has a side-effect solutions page contributed to by other blood cancer patients - Side Effect Solutions

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