Speaker advises caution in adding mAbs upfront in MM
NEW YORK, NY—Despite the attraction of incorporating monoclonal antibodies (mAbs) into upfront therapy for multiple myeloma (MM), a speaker at Lymphoma & Myeloma 2017 suggested mAbs are “not quite ready” for this use.
MAbs, particularly daratumumab, have shown single-agent activity in refractory MM and have been feasibly added to proteasome inhibitors and immunomodulatory drugs.
MAbs may even have the potential to enhance induction and shorten the time to minimal residual disease negativity.
“So the tendency is to simply add them to frontline therapy,” said the speaker, Joseph Mikhael, MD, from Mayo Clinic Arizona in Scottsdale.
However, he noted that there is little long-term experience with these agents.
“I’m going to suggest to you that they’re not quite ready [for upfront use] but will likely be ready in the future,” Dr Mikhael said. “We’ve had such a revolution in myeloma the last decade that it’s just easy for us to say, ‘Oh, throw it in there, just like we did, frankly, with rituximab in the lymphoma days. We added it to CVP, we added it to CHOP, we added it to bendamustine. It didn’t matter what we added it to, it just upgraded the response.”
“And, sometimes, I think we have the same approach with daratumumab or elotuzumab or some of the other mAbs that we have. I think we just have to do so cautiously.”
At present, the combination of a proteasome inhibitor and an immunomodulatory drug are the standard of care upfront in transplant-eligible and -ineligible MM patients.
Daratumumab plus KRd
Dr Mikhael described the experience of daratumumab added to carfilzomib, lenalidomide, and dexamethasone (KRd) in patients with newly diagnosed MM in the MMY1001 study.
Twenty-two patients were enrolled on the study, 91% achieved a very good partial response (VGPR) or better, and 43% achieved a complete response (CR). The depth of response improved with the duration of treatment.
Eight patients (36%) discontinued treatment.
Dr Mikhael emphasized that the preliminary data included very small numbers.
“There is a little bit of a yellow flag that pops up here,” he added, “when I see that 36% discontinued treatment, even in small numbers.”
The safety profile was consistent with previous reports for daratumumab or KRd.
The most common hematologic grade 3-4 treatment-emergent adverse events (AEs) occurring in 30% or more of patients were lymphopenia (64%), thrombocytopenia (9%), anemia (9%), leukopenia (9%), and neutropenia (14%).
Diarrhea (14%), cough (5%), fatigue (5%), insomnia (5%), and increased ALT (9%) were the most common grade 3-4 nonhematologic treatment-emergent AEs occurring in 30% or more of patients.
The treatment had no adverse impact on stem cell collection.
Elotuzumab plus VRd
Turning to elotuzumab in combination with bortezomib, lenalidomide, and dexamethasone (VRd), Dr Mikhael reviewed the phase 2a study (NCT02375555) presented at ASCO 2017 (abstract 8002).
Forty-one patients were enrolled on the study.
The overall response rate after 4 cycles was 100%, with 24% achieving a CR, 47% achieving a VGPR, and 29% a partial response.
Fatigue (60%), neuropathy (55%), musculoskeletal/joint pain (55%), infection (50%), back/neck pain (48%), diarrhea (45%), edema (38%), constipation (38%), cough (35%), mood alteration (35%), rash (35%), and insomnia (30%) occurred in 30% or more of patients.
“So again, not shocking,” Dr Mikhael said, “there was fatigue, there was neuropathy, and there were infections in 50% of patients.”
Grade 4 or greater AEs included thrombocytopenia, hyperglycemia, sepsis, cardiac arrest, and respiratory failure.
“However, here, [we have] maybe not even a yellow flag but a red flag of caution that there were 2 patients who died,” Dr Mikhael noted.
