Dr Usmani Discusses Methods for Managing Patients With Newly Diagnosed MM
Saad Z. Usmani, MD, MBA, FACP, Levine Cancer Institute, North Carolina, presented methods for managing transplant ineligible newly diagnosed multiple myeloma (NDMM) for elderly patients at the 2021 virtual Leukemia, Lymphoma & Myeloma Congress.
Dr Usmani highlighted a treatment paradigm for NDMM, where patients who are eligible for autologous stem cell transplant (ASCT) receive induction therapy, then autologous transplant consolidation, maintenance, and treatment for relapsed disease. For those who are ineligible, initial therapies are provided with strategized supportive care options to follow.
“It’s important to recognize myeloma primarily affects older patients. We need to engage in geriatric assessments, which is an ongoing process during care. This requires reaching out to our experienced colleagues to develop and implement appropriate treatment plans with regular monitoring and revising,” explained Dr Usmani.
To perform a comprehensive geriatric assessment for NDMM, Dr Usmani recommended having an open discussion with patients to identify activities during daily life, physical performance and health, psychological status, and socioeconomic wellbeing.
There are two physical performance tests recommended for conducting a comprehensive geriatric assessment. Both the Short Physical Performance Battery and Time Up and Go tests are simple and fair in evaluating patient fitness.
Further, there are several standardized cognitive screening tests such as MMSE, Mini-Cog, MoCA, and CDT that can be incorporated into the assessment process.
Current NCCN regimens for non-transplant candidates include bortezomib, lenalidomide, and dexamethasone (VRd), daratumumab-Rd, and Rd alone.
The general approach for most ASCT ineligible patients involves RVd-Lite1 for 8 to 12 cycles with lenalidomide maintenance until progression.
“The SWOG S0777 trial led to the standard of care acceptance of RVd compared to Rd in patients without immediate intent for ASCT. This was a large, randomized, phase 3 study that showed the superiority of RVd in progression-free survival (PFS) and overall survival (OS),” confirmed Dr Usmani.
Further developments led to the RVd-Lite regimen, which was based on a phase 2 study that revealed significant improvements in overall response rates (86%), a median PFS rate of 35.1 months, and high tolerability with an admirable safety profile.
The ALCYONE trial evaluated daratumumab plus bortezomib, melphalan, and prednisone (VMP) in MM for PFS outcomes and yielded significant improvements in older patients. Although D-VMP prolonged OS in patients with NDMM ineligible for ASCT, Dr Usmani found daratumumab plus Rd to be a more optimal regimen.
“The phase 3 MAIA study was clinically relevant with an older patient population. 43% of patients were over the age of 75. Demographics and baseline characteristics were well balanced between treatment arms with a median duration of follow-up of 56.2 months. 42% of patients in the D-Rd and 18% of patients in the Rd arm remained on treatment,” continued Dr Usmani.
The study highlighted durable responses with D-Rd and significantly higher rates of complete remission in comparison to Rd alone. Notably, D-Rd provides an additional 28 months of follow-up with continued and deepened daratumumab therapy.
“D-Rd continued to demonstrate a significant PFS benefit at 52.5% versus 28.7% with Rd. The median PFS has still not been reached after 60 months with D-Rd. These data will provide a new PFS benchmark in patients with NDMM. We were impressed to observe D-Rd demonstrated a significant benefit in OS with a 32% reduction in risk of death,” explained Dr Usmani.
These data infer that continuous therapy outperforms fixed-duration therapy for older patients. Dr Usmani found that the future will likely sustain MRD driven clinical trials, however, this may change.
In regimens that contain mAb, clinicians should be mindful of infection risks. IVIg should be considered for hypogammaglobulinemia, and antibiotic prophylaxis should be considered for patients who have a history of frequent infections leading to NDMM diagnosis.
“In conclusion, RVd-Lite and DRd are appropriate standard of care choices. Older, frail patients can receive Rd alone. Geriatric assessments need to be incorporated in the care schema. We are awaiting future data of RVd-Dara (subQ), RD plus ixazomib, and Rd plus elotuzumab,” concluded Dr Usmani.—Alexa Stoia
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