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4yr
Immunotherapy Advances in Multiple Myeloma

The introduction of monoclonal antibodies to treat multiple myeloma (MM) is a major immunotherapy breakthrough. The most recent advances include the 2021 FDA approval of belantmab mafodotin-blmf, which is an anti-BCMA monoclonal antibody that is bispecific and binds to B-cell maturation antigen (BCMA). The next approval was idecabtagene vicleucel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR)-T cell immunotherapy. These treatments are indicated for adults with relapsed or refractory multiple myeloma after four or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and anti-CD38 monoclonal antibody. Some experts, however, anticipate utility in earlier lines of MM treatment. Others have expressed concern that use of these agents earlier in treatment could expose the patient to targeted antigens relatively early and thus impact retreatment with an immune-based treatment approach later on.

Moving forward, what role do you see for newly approved immunotherapies in the treatment of MM? What benefits/risks do you think these agents will offer? How do you counsel your patients on these immunotherapies?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534104/
https://www.nature.com/articles/s41587-021-00929-0
https://bloodcancerdiscov.aacrjournals.org/content/2/5/423
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-granted-accelerated-approval-belantamab-mafodotin-blmf-multiple-myeloma
https://www.ashclinicalnews.org/spotlight/charting-myeloma-immunotherapy-landscape/

  • 4yr
    Thanks, All, for the wonderful and insightful feedback! What are your thoughts about the potential for these agents used earlier in MM treatment negatively impacting retreatment with later immunotherapy?
  • 4yr
    The exact sequence unfortunately not known. It is nice to see the potential of have to see what the trials show as to where to sequence it. likely earlier than 4 th line I would imagine
  • 4yr
    Optimal sequencing of agents in MM is still undefined and evolving, but anticipate immune based therapy to eventually be used in earlier lines. Role for both ADC and CAR-T but not sure how prior Blenrep therapy would influence response to subsequent BCMA directed CAR-T treatment
  • 4yr
    thank you for the information
    Can it be used as a bridge to CAR T or transplant?
  • 4yr
    I think Abecma is likely to be more effective
    Blenrep tolerance is an issue
  • 4yr
    Blenrep has become more accessible to patients in the triple refractory setting (usually after xpovio in my practice) with the involvement of ophthalmology and better guidance on preventing and managing ocular side effects. Meanwhile, the manufacturing delays for Abecma are limiting its current usage to the “last-resort” setting after blenrep though this may change with time.
  • 4yr
    For me, Belantamab mafadotin is becoming much more used in the 3rd line setting after refractory to the triple-refractory IMID, PI, CD38. The question is whether CAR-T will be more accessible in the near future as there are serious access issues in our region. Hopefully, with approval of 2nd Car-T in near future it will be a more feasible option. Insurance issues will obviously play a major role too.
  • 4yr
    car-t adc and bispecific antibodies are indeed excellent options in later lines of treatment with survival advantage. These will eventually move to earlier lines.I am not sure what will be fate of current regimens being used today which are excellent options
  • 4yr
    The utilization of belamaf will be dramatically impacted by the availability of bispecific ab. All potential areas where belamaf can be used will see bsA encroaching and eclipsing and displacing belamaf. The one area belamaf could be used is bridging before CART and CART maintenance. The main issue with belamaf is the ocular toxicity and there does not seem to be a way around it.
  • 4yr
    Both Abecma and Blenrep are reasonable options for this patient, pros and cons of each approach should be always considered with patients involved in the decision making process.
  • 4yr
    Immunotherapy is generally well tolerated and is targeted therapy. I see monoclonal antibodies and bispecific antibodies as being used earlier in MM with better efficacy. BCMA is a very specific target and is cleaved, allowing for a marker to predict response as well.
  • 4yr
    BCMA directed treatments are becoming more standard as we are seeing more refractory patients. Blenrep is my treatment of choice, Abecma is a great option but still face logistical challenges in my area.
  • 4yr
    I agree with most the comments mentioned above- BCMA directed BiTE therapy or ADC as well as anti BCMA CAR-T therapy are likely to be mainstays for patients with R/R MM after exposure to Quad regimen- Dara-VRD as well as refractoriness to them.
    In addition, it will be interesting to see how Blenrep combination responses and MRD levels are, since that will help guide better PFS.
    In regards to early use and possible inability to use immune or CAR-T therapies later, the early data so far shows that you can still use BCMA directed CAR-T post Blenrep. So atleast for now, I do not foresee an issue there. CAR-T production and logistics ofcourse remain a concern and for patients who cant wait for 1month, bridging therapy will be very helpful
  • 4yr
    Post ASH DVRD will become standard of care ,my feeling is we will be using MRD to determine when to stop therapy and likely will not transplant as much as we are doing now
    bispecific anidies and car t cell may move into consolidation as data matures
    the cost of these therapies is prohibitive
  • 4yr
    Supplementing the best induction therapy (4 drug regimens which include daratumumab) with foreseen bring the novelty of BMCA directed Bite cells and CAR-t therapies to second line. early applications of novel therapies are likely to enhance survivals in those who are unable to acheive initial mrd negativity or who have early relapses.
  • 4yr
    Belantamab mafadotin is emerging an appropriate on label option for our MM patients after Daratumumab. Given the supply chains of CAR based therapy, we are using Belantamab more prominently. Appropriate use on label is essential, as well as collection or RWD.
  • 4yr
    I think both these medications are good advancements in mm. We should only use them on label currently and wait for trial data to move them up further. I do worry about antigen issues which may make other therapies not work well if patients are refractory.
  • 4yr
    I think the so-called BITES will be a major force in future myeloma therapy as they incorporate the efficacy of CART with the convenience off being off the shelf. The toxicity profile is similar to CART, jut less severe.
  • 4yr
    I believe that in the foreseeable future, immunotherapy agents may be a reasonable and efficient treatment option for patients in the earlier lines of treatment. We need to continue to evaluate the optimal treatment sequence and better understand if/how immunotherapy agents may impact any potential next line of treatment. The potential benefit of these agents is relatively high response rates that are durable. Neurological and CRS toxicities are obviously a possible toxicity. In general, I counsel my patients that these treatments are designed to more specifically target the malignant plasma cells.
  • 4yr
    I think both Abecma and Blenrep are acceptable in this scenario.
  • 4yr
    As I see it, by second line most of my patients will be quad refractory - two IMIDs, one PI and CD38. Thus by 3rd line, patients eligible for idecabtagene would be referred for this therapy. Since BMS is not up to speed with the production of the product, most pts would need salvage therapy. I am happy to use Balantamab in this situation which offers a different MOA and exciting ORR.

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