Side effects of various myeloma treatments—chemotherapy, bone-strengthening drugs, monoclonal antibodies, transplant—can be as bad or worse than the disease itself.  With the ever-growing range of treatment options, both minor and major side effects are part of the promise of potentially going into remission.  The good news is that physicians and nurses have the tools and experience to anticipate, avoid and treat these side effects.  Side effect mitigation is as important to patient care as every other part of treatment.

Drs. Craig Hofmeister and Suzanne Lentzsch discuss strategies and tips to help recognize and avoid adverse reactions to various treatments and procedures in the Myeloma Crowd Round Table Interactive Webcast held on December 19, 2020:

Craig Hofmeister, MD, MPH, Winship Cancer Institute, Emory University, Atlanta, GA: Side Effects of Bone Disease, Neuropathy, and IMiD-Related Rashes

• Majority of bone marrow is in vertebra (spine) and pelvis
• Osteoclast activity destroys bone, osteoblast builds bone, an ongoing, natural cycle
  • Zometa ® turns down the osteoclast activity
  • XGEVA ® (denusomab) starves the osteoclasts’ energy
• Overview of procedures to treat bone pain and fractures
• Zometa and XGEVA decrease risk of fractures
  • Unknown exactly how much to use in each patient
  • XGEVA and Zometa are approximately equal, XGEVA preferred for patients with kidney issues
  • Biggest risk is osteonecrosis of the jaw (ONJ)
• Neuropathy
  • Tingling, numbness and burning sensation of nerves
  • Generally builds with some therapies
  • Early communication is vital, with Velcade, if it doesn’t happen by 5th dose, one will not get neuropathy
  • To reduce, reduction of frequency is done first, then dose reduction
  • Be wary of vitamin treatments claiming to reduce neuropathy
  • Acupuncture has been shown to be effective in a small study
  • Massage, compression stockings, cocoa butter provide temporary relief
  • Cymbalta, neurontine, Lyrica can help
  • Opiates can help if severe, dosing is a challenge, fear of addition an issue
• Rashes caused by IMiDs
  • Rash does not indicate allergy
  • If rash develops, stop taking IMiD and take non-sedating antihistamines, pulse of steroids
  • Dose reduction is standard
• Shingles
  • Can precede myeloma diagnosis
  • Velcade, daratumumab and CAR T have increased risk of shingles
  • Can be treated with acyclovir and valacyclovir
  • Shingrix vaccine after transplant or in maintenance is effective
  • If it affects eyes, seek immediate treatment and ophthalmologist evaluation

Suzanne Lentzsch, MD, PhD, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY: Side Effects of Myeloma Treatment/Insights into COVID

• Why is there increased rate of infections in myeloma
  • Inhibits B cell function
  • T cells are effected and work less effectively causing neutropenia
  • Age, frailty, organ damage, steroids cause higher blood sugar
• Even patients with MGUS have increased risk of infections
  • UK study demonstrated lower infection rates with use of levofloxacin, but there GI side effects
• COVID-19
  • Three stages: I has mild symptoms in upper respiratory tract; II has pulmonary effects including shortness of breath; III is hyperinflamation phase
  • Remdesivir helps in stage II
  • Low number of lymphocytes and older age is high risk factor
• Spanish study compared COVID-positive myeloma patients with non-cancer patients
  • Myeloma patients had higher risk of needing ventilation which led to higher mortality
  • Mortality in myeloma patients was higher in males, patients >65 years old, with active disease, and with renal disease comorbidity
• Recommendations for maintenance therapy during pandemic
  • Treatment of myeloma cannot be neglected during pandemic, can be adjusted to limit possible exposure
  • Extend access to lenalidomide (Revlimid ®)
  • More use of telemedicine (or telehealth) visits, in-home blood draws and oral drugs
  • High-risk patients should continue with RVd maintenance
  • If COVID-positive, interrupt maintenance to treat virus
  • Patients considering transplant must balance risk of COVID with risk of transplant
  • Caregivers should get vaccine when available
  • Wear a mask!
• CAR T cell therapy side effects
  • Cytokine release syndrome (CRS)
  • Immune effector cell-associated neurotoxicity (ICANS) is a CAR T toxicity that can cause changes in mental status, confusion, delirium, and seizures
  • Cytopenias, prolonged low number of platelets and white blood cells
• CRS occurs when immune system is overstimulated, common but increasingly more treatable
  • Tocilizumab, a monoclonal antibody that blocks IL-6 signaling, is effective to restore normal numbers
  • Steroids also used for severe side effects, but can block anti-myeloma effect
  • Side effects normally take effect 7-14 days after therapy, proper treatment brings them back down
  • CRS severity correlates with disease burden; the more disease, the greater the possibility of side effects
• Risk assessment with physician critical in making decisions

Audience Questions & Answers

• 0:21 - Can one get shingles if one has had the shingles vaccine?  After which therapies should one have it?
• 2:35 - Does one need acyclovir after a CAR T procedure?
• 4:30 - Can the Shingrix vaccine be used by someone who has had an allo transplant?
• 6:06 - At what point should one consider halting medication due to neuropathy?
• 9:16 - Does Revlimid cause neuropathy?
• 11:31 - If Velcade-caused neuropathy occurred in front line treatment, should one reconsider using it after relapse(s)?
• 13:22 - What are your opinions about the COVID-19 vaccines for myeloma patients?
• 18:35 - Can Velcade be replaced with anything else besides another proteasome inhibitor to avoid neuropathy, especially if hand sensitivity is important for professional reasons?
• 19:47 - Are the side effects of different bisphosphonates (bone strengtheners) the same?  [Learn more about this in the Myeloma Crowd Round Table on Bone Issues here.]
• 23:20 - Where and when will patients get a COVID vaccine?  Is there a difference between the two vaccines available now?
• 26:01 - Are there any specific medications that cause headaches?
• 27:40 - How long after an anti-BCMA CAR T therapy does one maintain maximum benefit?  How long does immunosuppression last?
• 31:25 - When should one use IV Ig, does it help against COVID?
• 33:03 - Re: Revlimid-related neuropathy.  At what point should one consider stop using it if that is the suspected cause?
• 33:50 - What are some anticipated side effects of the combination of selinexor, bortezomib (Velcade) and dexamethasone?  Does the combination of selinexor and Velcade reduce neuropathy?
• 37:10 - Would a patient on Revlimid be better prepared to fight COVID or respond to a vaccine?
• 40:03 - How would one determine if one has responded to a COVID vaccine?
• 42:00 - How does one best manage dexamethasone?
• 46:34 - Director of Product Todd Foster and Patient Engagement Lead Ana Sahagun describe the side effects solutions feature of HealthTree profiles.

Questions Answered by Dr. Hofmeister in Chat Forum

Neuropathy

1. Is there anyway to slow the progression of Velcade-related neuropathy?  One doctor said that B12 injections plus gabapentin can help, another said nothing can help.  A third said early trial results show that Cymbalta might help.  How can I know when to stop Velcade before I develop pain that will last my whole life?

Answer:  There is no known way to slow the progression of Velcade-related neuropathy other than lowering the dose or stopping further exposure to it.

2. Regarding neuropathy, can acupuncture help with the pain or prevent progression?

Answer:  In a small study of 20 patients, it decreased pain and improved function when given twice a week for a month then weekly.  [Dr. Hofmeister discusses this in greater detail in his presentation above.]

3. Revlimid and Velcade did not work for me. Is carfilzamib (Kyprolis) less likely to produce neuropathy?

Answer:  MUCH less likely to cause neuropathy.

4. I am diabetic with myeloma.  I had mild neuropathy in one foot related to my diabeties.  I am one year into my myeloma diagnosis and am in remission.  During treatment I was on VRd.  Now I have increasing neuropathy in both feet.  My oncologist feels that the neuropathy is diabetes-related.  But neuropathy got worse with myeloma treatment.  How do I control the neuropathy when dealing with both MM and diabetes?

Answer:  I would avoid Velcade and thalidomide forever and ever.

5. With a combination treatment like VTd (Velcade thalidomide, dexamethasone) how does one determine which is responsible for peripheral neuropathy and how to modify treatment ?

Answer:  I wish I knew.  I don’t use thalidomide anymore as its neuropathy is such a pain.  When I have used this regimen in the past, I would decrease the dose of both Velcade and thalidomide because I didn’t know which was causing the problem.

Shingles

6. If you get the Shingrex vaccine, is it necessary to stay on acylovir?  If so, should the dosage be reduced?

Answer:  We don’t know the effectiveness of Shingrix in patients who continue on immunosuppressive therapy, such as VRd.  It is effective in patients younger than 50 who are not on therapy and is also effective within three months of autologous transplant.  It’s a VERY effective vaccine, but we don’t know everything.  I tell patients that are on single drug Revlimid maintenance that they can stop acyclovir after receiving the second Shingrix vaccination.  Those patients on multi-drug therapy I advise to at least take acyclovir daily if they have received both doses of Shingrix.

7. Should acyclovir be continued after Shingrix for a person in remission and on 10 mg of Revlimid two years after SCT? If so, at what dose?

Answer:  I wouldn’t.

8. I've been diagnosed with smoldering MM. Would you recommend getting a shingles vaccination?

Answer:  Yes if you are less than 50.

9. Is valacyclovir equally effective as acyclovir for preventing shingles?

Answer:  Yes.

10. I’m in remission one year after transplant.  I have been told the Shingrix vaccine has not been approved by the FDA for patients like me yet.

Answer:  You’ll get it paid for if you are less than 50.

COVID Vaccines

11. If a patient is within one month of stem cell collection for a potential ASCT, when, if at, all should she receive a COVID vaccine when it is available?

Answer:  Great question.  My suggestion is to never turn down a Moderna or Pfizer COVID vaccine if you can get it.  Since you’re in the midst of treatment, you may not have a good response, but no matter what I wouldn’t turn it down.  That said, it will be MUCH higher value if you can delay until at least 3 months after autologous transplant.

12. Will the vaccine work if we are on chemotherapy?

Answer:  We don’t know yet.

13. Should myeloma patients get IVIG infusions during this pandemic?

Answer:  Patients that are high risk of contracting COVID that have low serum IgG levels, i.e., IgG < 400 mg/dL, might benefit from IVIG.  But IVIG is not without side effects so an open and honest discussion, incorporating your infection history seems the most prudent way forward.

14. With the new COVID-19 vaccine now out, a few patients had a bad side effect and some had severe allergies which caused this reaction.  I want to take the vaccine, I have myeloma, but I have allergy to adderall and some other medicines line gamadex and gamunex.  Should I get the vaccine?

Answer:  Yes.  Be sure to stay at the vaccine administration area for 15-30 mins after receiving the vaccine so that you can quickly receive medications for an allergic reaction in the unlikely case that it happens.

Skin-Related Side Effects

15. I have had severe burning neck and upper body skin pain without any visible skin changes after starting Dara-Rd (Darzalex faspro, Revlimid, dexamethasone) as a sixth or seventh line of therapy.  I was on Revlimid for a short time five years ago, and IV Darzalex for more than a year about three years ago without problem.  Have you seen this as a severe problem?   Do you think neuropathy may be exacerbating a mild symptom (i.e. any role for trying gabapentin)?

Answer:   That’s a tough one.  I don’t know if it’s a Revlimid-related rash that is causing pain.  Could it be a radiculopathy from nerve compression of your cervical spine?   Yes, gabapentin (neurontin) or any other adjunctive medication might help.

16. IMiD related rashes are known about.  Is it the same for carfilzomib (Kyprolis and are the remedies the same?

Answer:  No.  Kyprolis (carfilzomib) generally doesn’t cause a rash and this might be more of an allergic episode.

17. I typically get a winter dry skin rash on torso. I am in second month of RVd after my recent myeloma diagnosis.  My winter rash seems more widespread.  How to I tell if this is rash due to Velcade?

Answer:  Remember to use a thick moisturizer twice daily like Bag Balm or Eucerin.  The rash is very, very, very unlikely to be Velcade-related.

18. After my ASCT, I had bad burning in my big toes when lying down that kept me awake.  After one week of 200 mg alpha lipoic acid, B6 and B12 it was gone.

Answer:  I wish more of my patients had this response.  This is great!

19. I’ve read recently about studies concluding that anticholinergic drugs like Claritin can contribute to dementia.  On my specialist’s instruction, I was taking a daily dose of one pill (10 mg) with my Revlimid to prevent the rash.   After reading the literature I asked to decrease my dose and have cut it in half.  The decreased dose is working for me but I am still concerned about long term cognitive effects of this drug.  Can you comment on this?

Answer:  I think decreasing anticholinergic drugs makes good sense.  I’d try life without Claritin to see if you develop a rash.  Let’s not forget that Revlimid does get into the cerebrospinal fluid and can affect mentation.  I don’t know if it contributes to dementia.

GI Side Effects

20. Does reducing the dosage of Revlimid reduce GI side effects? What is the effect of reduced dosage on length of remission?

Answer:  We don’t know if dose reduction reduces effectiveness for doses of 100-400 mg Thalomid, 10-25 mg Revlimid, and 2-4 mg Pomalyst.  Below these lowest doses, it will reduce effectiveness in most patients but not every patient.  Reducing the dose of Revlimid does reduce GI side effects.  For Revlimid-related diarrhea, I usually use Imodium first, and welchol for those patients with continued diarrhea.

Cardiac Side Effects

21. Are there any precautions to be aware of for a myeloma patient who has previous heart attack and heart failure?  Can the treatment effect the heart?

Answer:  Yes, Kyprolis (carfilzomib) can cause shortness of breath and cardiac damage in a small proportion of patients.  No predisposing factors have been identified.

Drug Treatment Side Effects

22. I just began taking Selinexor-Vd.  What side effects can I expect?

Answer:   Things that I think about are Selinexor-related side effects include nausea, diarrhea, and fatigue.

23. I’m on 4mg Dara-Pd and am in cycle 16 after May 2018 diagnosis.  I need a cholecystectomy due to cholecystitis.  My oncologist says I need to be off drugs for 6 weeks.  Do you agree?

Answer:  Generally I recommend patients stop Dara-Pd at least one week prior to surgery and for two-to-three weeks after.

24. What is the best way to deal with fatigue and the brain fog that comes along with treatment?  I am on Dara-RD.  The "crash" from the dex and the brain fog are the most bothersome for me right now.

Answer:  Generally I lower the dose of dexamethasone to 8-12 mg weekly in patient who continue Dara-Rd.  After that, Revlimd is known to cause “chemo brain” and it can be mitigated by a lower dose.

Bone-Strengthening Drugs

25. Is there any recommendation regarding getting Zometa/biphosphonates after CAR T cell therapy?

Answer:  I would only get these drugs if the myeloma does NOT respond to the CAR T.

26. What about pamidronate?

Answer:  Nothing is wrong with pamidronate, but it’s less convenient than Zometa so it’s rarely used

27. Can necrosis be healed with the liquid swishing product?  You mentioned chlorhexidine.  I recently had a tooth extracted and may be experiencing necrosis. I have been using this product.  Or, what would you recommend as a next step.  Fortunately, it has improved and not that bothersome.

Answer:  Osteonecrosis of the jaw (ONJ) might improve with chlorhexidine twice daily.  This is the only intervention I use for patients with ONJ

28. Do you recommend high dose vitamin D and/or OSCAL+D when a patient is in remission and on maintenance therapy?

Answer:  I do not.

General

29. Is a dramatic reduction in mobility always seen in new myeloma patients starting treatment?

Answer:  It is not always seen, but most patients at the time of diagnosis are really at their worst, ‘the wheels have fallen off the wagon’ with fractures, anemia, and kidney failure.  The hope is that with treatment symptoms improve and things get better.

30. I  have smoldering multiple myeloma-diagnosed about 4 yrs ago,and have never received treatment. is that unusual??

Answer:  No.  That’s probably the most common situation

31. Could CAR T therapy be used in a patient who has had an autologous and an allogeneic transplant?

Answer:  You won’t qualify for most clinical trials for a CAR T in myeloma, but ideally once BMS commercial CAR T (bb2121) is approved, then yes.  [FDA approval for bb2121 is expected in March/April 2021.]

Thanks to our Round Table sponsors

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