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4mo
Expanding Horizons in Multiple Myeloma: CD38 Antibodies in Transplant-Eligible Patients

The FDA recently approved daratumumab and hyaluronidase-fihj (subcutaneous CD38 antibody) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for induction and consolidation in newly diagnosed multiple myeloma (MM) patients eligible for autologous stem cell transplant (ASCT). The approval was based on clinical trial results (NCT03710603) that demonstrated a significant reduction in disease progression or death by 60% with CD38-VRd compared to VRd alone. Common adverse reactions included neuropathy, fatigue, and upper respiratory infections, among others. The efficacy and tolerability of CD38 antibodies continue to expand their role in optimizing MM treatment outcomes.

How does the addition of CD38 antibodies reshape the treatment landscape for transplant-eligible multiple myeloma patients? What factors should clinicians consider when selecting induction therapies for this patient population?

  • 4mo
    Based upon the IMROZ trial of isatuximab-VRd versus VRd in transplant ineligible, which led to the FDA approval of isa-VRd in frontline AND the completed Cepheus trial of dara-VRd versus VRd, abstract presentation, a quadruplet appears to be the standard of care for transplant ineligible patients. That stated, even though there is an abbreviated schedule for bortezomib (discontinued after 6 cycles), there is still a concern for peripheral neuropathy in these patients. Forthcoming will be isa and dara-KRd trials which will eliminate the concern for peripheral neuropathy. The Perseus trial led to the approval of dara-VRd for transplant eligible patients. Soon, isa-VRd and dara-KRd will also be included in this group. Indeed, they are listed in the NCCN guidelines even though not FDA approved other than dara-VRd.
  • 7mo
    CD38 ab is a must in the first line, regardless of transplant eligibility. All evidence points toward improved outcomes with CD38ab in the first line. In fact, I have been using Dara-RVD in TE pts and Dara-RD in T-I and now Isa-RVD in T-I pts. The data from the recent CD38 ab trials have been practice changing. It remains to be seen if there is utility for CD38 in relapse now, after CD38 utilization in first line and if the OS would be impacted after pts fail CD38 or are exposed to CD38 ab in the first line.
  • 7mo
    i think 4 drug combo is new SOC, not sure pfs increase is going to be meaningful as feel that bi specifics will move in sooner shortly
  • 7mo
    after FDA approval, daratumumab and hyaluronidase-fihj +VRd will be used in more patients with MM who are eligible for SCT.
  • 8mo
    I have been using this regimen in front line therapy for a while now. Quad is my go to in this space
  • 8mo
    CD38 antibodies are now used in all pts, transplant eligible and ineligible. Makes the role of transplant more unclear given added benefits of darzalex in pts eligible for transplant
  • 10mo
    CD38 antibody combination has become the standard first line treatment for myeloma
  • 10mo
    these are now a standard for first line option so always use them as add on. prefer D-VRD for all
  • 10mo
    anti CD38 has been the backbone of BMT eligible MM pts for a while, I have used D-RVD for a while prior to FDA approval
  • 10mo
    I use DaraVRD as 1st line in transplant eligible patients
  • 11mo
    I think anti-CD38 quads are standard of care at this point for transplant eligible MM patients, and should be used in select transplant ineliglble patients.
  • 11mo
    I have been using DaraVRD in my transplant eligible pts
  • 11mo
    If a patient is transplant eligible, then they would certainly be eligible for this quad therapy. Dara-VRD Is considered the standard of care in transplant, eligible patients. Dara Is very well tolerated, and it really does not add any significant toxicity in the real world when added to VRD so it was not a very difficult addition to our previous triplet induction program
  • 1yr
    I am using a Quad regimen with CD 38 antibodies in the first line setting for transplant eligible and ineligible patients.
  • 1yr
    Dara-VRd has established itself as SOC for frontline in TE patients, except in certain circumstances. Dara is tolerable, convenient and adds a depth of response that was previously not seen. Patients still, however, should go to transplant after initial therapy.
  • 1yr
    Dara-VRd has established itself as SOC for frontline in TE patients, except in certain circumstances. Dara is tolerable, convenient and adds a depth of response that was previously not seen. Patients still, however, should go to transplant after initial therapy.
  • 1yr
    I have been using DVRd to almost all ( except frail/ old and those who cannot toelrate quadruplet due to concern for cytopenias/ poor hepatorenal function etc) regardless of their trasnplant eligible status- and i believe DVRd should be SOC.
  • 1yr
    D-RVD has been now the standard of care in all eligible patients, whether or not they are transplant candidates.
  • 1yr
    For transplant eligible patients, Dara-RVd would be considered the standard of care. This treatment offers the highest response and the most durable PFS. Regardless of the response to treatment, the patient would still benefit from addition of auto transplant for consolidation of gains and to prolong relapse free survival.
    Factors to consider when selecting induction therapies are - transplant eligibility, age, performance status, organ function etc.
  • 1yr
    I believe CD38 Ab should be used in the first setting - either in doublet if poor PS, or triple or quad therapy based on there other co-morbidities and PS
  • 1yr
    This is standard of care for the most part. Dara-VRD
  • 1yr
    I would always use the best therapies for patients upfront so Dara moving up is standard of care and is used. This definitely can have profound downstream impacts on treatment selection in the relapsed setting.
  • 1yr
    Use darzalex for all transplant eligible patients in a quad, and for transplant ineligible in triplet
  • 1yr
    It really seems like old news, as I have been using the quad for years in both transplant eligible and ineligible.
  • 1yr
    today, using a 4 drug regimen consisting of D-VRD with CD 38 inhibitor has been the SOC ofr past 2 yrs
  • 1yr
    Agree with the above comments in that the treatment landscape has essentially transitioned to quadruplet therapy for transplant eligible patients. Would argue that this generally holds true for standard and high risk patients (perhaps with istuximab based and incorporation of carfilzomib if able). Other factors to consider would include concerns with certain agents in particular patient populations (such as bortezomib with neuropathy, carfilzomib with cardiovascular disease, etc).
  • 1yr
    On basically everyone, will start with dara-RVd. Pretty easy decision to make right now, whether going to transplant or not.
  • 1yr
    We have multiple phase 3 studies showing improved efficacy for quads therapy in first line. In my opinion, it should be standard of care to offer all transplant eligible and selected transplant ineligible a quads regimen including anti vd38 antibodies in first line irrespective of cytogenetics.
  • 1yr
    This study confirms the benefit of using a quad regimen in the treatment of myeloma. It is now the standard of care. Factors that may modify this includes performance status, preexisting neuropathy, renal function, molecular profile, etc
  • 1yr
    using this regimen in all comers now, transplant eligibility determined later, mostly for rapid, deep responses to treatment.
  • 1yr
    I have been using Dara-VRd as induction before HDT-ASCT, for almost 3-4 years, very well tolerated with high responce rates and is the standard of care, if they are not transplant eligible using DRD as the preferred regimen, haven't used the quadruplet with Isatuximab in transplant ineligible patients yet.
  • 1yr
    This has already been the standard of practice for many months. I think this just puts the capstone on the standard of care.
  • 1yr
    With approval of Dara-VRd for transplant eligible patients and Isa-VRd for transplant ineligible patients, the quadruplet appears to be the current standard of care over triplets. That stated, it is not clear if the actual survival is superior by giving the anti-CD38 upfront OR if it can be used in the relapse setting which is still a very powerful agent. The phase 3 trials compared Dara/Isa-VRd versus VRd alone and then concluded that the overall survival was superior in the quadruplet. However, they do NOT have any data on VRd triplet followed by an anti-CD38 mAb salvage therapy. Unless ALL of the patients in the Phase 3 control arms received dara as salvage therapy, they cannot state that there is an overall survival advantage.
  • 1yr
    use quad or triplets front line ,higher mrd neg status with combo
  • 1yr
    i think we are starting to use them in the forefront and in 1st line treatment given the data. this will of course lessen it's use in later lines. we need to consider toxicity and also its use with other drugs in combo regimens. also need to consider goals of care as well. logistics are to be considered in terms of administration as it's IV and also sub cu formulations. i believe them to be very effective drugs
  • 1yr
    Dara-VRd is standard of care for induction prior to HDT-ASCT, adopted long before FDA approval.
  • 1yr
    Essentially this is the standard of care. We need to be using quads unless performance status doesn’t allow.
  • 1yr
    I am using CD38 antibodies in the 1st line setting for ALL my myeloma patients. Usually part of a triple or a Quad regimen.

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