The multiple myeloma treatment paradigm has seen an assortment of therapeutic advances in recent years with agents that have demonstrated the ability to extend survival in patients and improving disease outcomes. However, the severity of the disease continues to linger without a cure, calling for oncologists to take new approaches to ensure that patients do not lose benefit while on treatment.
During a presentation at the National Comprehensive Cancer Institute (NCCN) 2020 Virtual Congress: Hematologic Malignancies, Shaji K. Kumar, MD, explained that each case of multiple myeloma requires a long-term strategy that starts with a strong approach in the frontline setting.1
Treatment Options in the Myeloma Paradigm
Once patients are diagnosed and stratified for risk, those who are eligible for stem cell transplantation (SCT) are eligible for consideration of induction, consolidation, and maintenance therapy cycles, said Kumar, who is medical director of the Clinical Research Office at the Mayo Clinic Cancer Center in Rochester, Minnesota. Patients who are ineligible for SCT, however, can only receive induction therapy followed by continuous systemic treatment. In addition, options vary for patients at their first through fourth relapse and beyond with all therapeutic options selected based on patient’s tumor burden.
Triplet Therapy for Transplant-Ineligible Newly Diagnosed Multiple Myeloma
The phase 3 SWOG S0777 [NCT00644228] trial demonstrated results that have informed decision making for frontline triplet therapy using a proteasome inhibitor plus an immunomodulatory drug. The study showed that the addition of bortezomib (Velcade) to lenalidomide (Revlimid) and dexamethasone (VRd) can significantly improve overall survival (OS) and progression-free survival (PFS) in patients with newly diagnosed myeloma who were not planned for immediate SCT with acceptable toxicity.2
The VRd regimen was compared with that of lenalidomide and dexamethasone alone (Rd). The trials primary end point was PFS using a prespecified one-sided stratified log rank test. Other end points explored in the study were OS, overall response rate (ORR), and safety.
The median PFS observed with the VRd regimen was 43 months versus 30 months with the Rd regimen. The stratified HR for the difference between the 2 arms was HR, 0.712; 96% CI, 0.56–0.906; one-sided P = .0018). The median OS was 75 months in the VRd arm compared with 64 months in the Rd arm (HR, 0.709; 95% CI, 0.524-0.959; two-side P = .025).
The superiority of VRd was significant and remained so, even when tested against other regimens. For example, the combination of carfilzomib (Kyprolis) plus Rd (KRd), as observed in the phase 3 ENDURANCE (E1A11) trial (NCT01863550). In the study, KRd did not improve survival over VRd with a median PFS of 34.6 months (95% CI, 28.8-37.8) versus 34.4 months (95% CI, 30.1 to not evaluable [NE]), respectively (HR, 1.04; 95% CI, 0.83-1.31; P =.742), according to results from the second interim analysis presented at the 2020 American Society of Oncology Virtual Annual Meeting and simultaneously published in the Lancet Oncology.3