SOHO 2026: Key Updates Across the Multiple Myeloma Continuum

Posters presented at the 2026 Society of Hematologic Oncology (SOHO) Annual Meeting detailed a range of updates spanning the multiple myeloma treatment continuum. Sessions covered a final, 6-year analysis reinforcing quadruplet therapy in transplant-ineligible newly diagnosed disease, provided real-world guidance for safely moving bispecific antibody step-up dosing into the outpatient setting, and strengthened the case for earlier use of CAR T-cell therapy in relapsed/refractory disease.

From data supporting daratumumab (Darzalex)-based quadruplet regimens to consensus recommendations for administering T-cell–engaging therapies outside the hospital, here are some key takeaways from posters presented at this year’s meeting.

CEPHEUS Reinforces D-VRd as Standard of Care in Transplant-Ineligible Multiple Myeloma

Adding daratumumab to bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (D-VRd) continued to produce deeper and more durable responses than bortezomib, lenalidomide, and dexamethasone (VRd) alone among transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), according to the final analysis of the phase 3 CEPHEUS trial (NCT03652064).¹

The analysis focused on the transplant-ineligible subpopulation of CEPHEUS after a median follow-up of 76.0 months. This group included 289 of the trial’s 395 patients, who were a median age of 72 years; approximately 76% of patients were 70 years or older, and 30% were 75 years or older.

At the 10^–5 sensitivity threshold, overall minimal residual disease (MRD) negativity with a complete response (CR) or better occurred in 61.1% of patients who received D-VRd (n = 144) compared with 40.0% of those who received VRd (n = 145; OR, 2.35; 95% CI, 1.47-3.77; P = .0004). Findings were similar at the 10^–6 threshold (46.5% vs 27.6%, respectively; OR, 2.27; 95% CI, 1.39-3.71; P = .0010).

Median progression-free survival (PFS) was not reached with D-VRd vs 50.20 months with VRd, and 72-month PFS rates were 59.3% and 38.3%, respectively (HR, 0.55; 95% CI, 0.39-0.78; P = .0007). Overall survival (OS) numerically favored D-VRd (HR, 0.84; 95% CI, 0.57-1.24), an effect that strengthened when deaths related to COVID-19 were censored (HR, 0.74; 95% CI, 0.49-1.12); the trial was not powered to detect a statistically significant OS difference.

No new safety signals emerged with longer follow-up, and fewer patients discontinued treatment because of a treatment-emergent adverse event with D-VRd than with VRd (9.7% vs 23.2%).

“[T]he final CEPHEUS analysis results reinforce D-VRd as the standard of care for patients with [transplant ineligible newly diagnosed multiple myeloma] as it provides deeper and more durable responses than VRd,” lead study author Saad Z. Usmani, MD, MBA, FACP, FASCO, chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center, wrote with coauthors in the poster.¹

Expert Panel Backs Outpatient Step-Up Dosing for Bispecific Antibodies in Multiple Myeloma

A modified Delphi (mDelphi) panel of US-based hematologist-oncologists and pharmacists reached consensus on how to safely administer step-up dosing (SUD) of the bispecific antibodies teclistamab-cqyv (Tecvayli) and talquetamab-tgvs (Talvey) in the outpatient setting for patients with relapsed/refractory multiple myeloma, according to findings from the NORTHSTAR study.²

The panel comprised 15 US providers, 7 hematologist-oncologists and 8 pharmacists, leading bispecific antibody programs in academic (n = 3) and community (n = 12) settings; 9 panelists had prior experience with outpatient step-up dosing for teclistamab or talquetamab. Over 3 rounds—90-minute semi-structured interviews, an online rating survey, and a revised re-rating survey—panelists rated 156 preliminary consensus statements on a 5-point Likert scale, with consensus defined as at least 80% concordance. Sixty-six statements achieved consensus in the second round; a third round was ongoing at the time of presentation.

The resulting statements addressed patient eligibility; access-to-care requirements such as proximity to the administering site and a designated emergency department capable of managing cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS); and defined roles for the care team, including hematologist-oncologists, advanced practice providers, on-site pharmacists, and social workers or financial coordinators. The statements also spanned eligibility determination, treatment-day dosing, and adverse event monitoring. The panel also outlined grade-based management pathways for CRS and ICANS, including specific criteria for escalation to inpatient admission, and a patient and caregiver education package covering premedications, home symptom-monitoring equipment, and emergency department guidance.

“Experts support the safe and feasible implementation of outpatient step-up dosing for teclistamab or talquetamab for appropriately selected patients with [relapsed/refractory multiple myeloma. The resulting consensus-based implementation guide will provide practical guidance on patient selection, AE monitoring and management, education and care coordination to support implementation of outpatient step-up dosing across diverse clinical settings,” lead author Muhamed Baljevic, MD, associate professor of medicine and director of plasma cell disorders research at Vanderbilt-Ingram Cancer Center, wrote with coauthors.² “Accordingly, the implementation guide is expected to improve the ability of US health care providers to operationalize outpatient step-up dosing, optimize health care resource utilization, and expand patient access to teclistamab or talquetamab.”

How Do BCMA-Directed CAR T-Cell Therapies Compare in Relapsed/Refractory Disease?

A systematic review and meta-analysis of randomized phase 3 trials showed that BCMA-directed CAR T-cell therapy produced significantly longer PFS than standard regimens in relapsed/refractory multiple myeloma, reinforcing the case for using cellular therapy earlier in the treatment course rather than reserving it for heavily pretreated disease.³

Investigators pooled data from 805 patients across 2 randomized phase 3 trials: KarMMa-3 (NCT03651128), which compared idecabtagene vicleucel (ide-cel; Abecma) with investigator-selected standard regimens in patients who had received 2 to 4 prior lines of therapy, and CARTITUDE-4 (NCT04181827), which compared ciltacabtagene autoleucel (cilta-cel; Carvykti) with pomalidomide (Pomalyst)-based therapy in patients who had received 1 to 3 prior lines and were refractory to lenalidomide (Revlimid).

PFS significantly favored CAR T-cell therapy in both trials (KarMMa-3 HR, 0.49; 95% CI, 0.38-0.65; CARTITUDE-4 unweighted sensitivity estimates HR, 0.40; 95% CI, 0.29-0.55). In the pooled random-effects analysis, CAR T-cell therapy was associated with a 55% reduction in the risk of progression or death compared with standard regimens (HR, 0.45; 95% CI, 0.37-0.55), with no observed heterogeneity between trials (I² = 0%). Both trials also showed substantially higher overall response rates (ORR) and CR-or-better and MRD-negativity rates with CAR T-cell therapy; in CARTITUDE-4, for example, ORR was 84.6% with cilta-cel vs 67.3% with standard therapy, and the CR-or-better rate was 76.9% vs 24.2%, respectively.

Updated CARTITUDE-4 follow-up showed a statistically significant OS benefit with cilta-cel (HR, 0.55; 95% CI, 0.39-0.79), with a 30-month OS rate of 76.4% vs 63.8% with standard therapy. OS findings in KarMMa-3 were harder to interpret, the investigators noted, given that approximately 56% of patients randomly assigned to standard therapy crossed over to receive ide-cel (HR, 1.01; 95% CI, 0.73-1.40). CRS and neurotoxicity were common with CAR T-cell therapy across both trials but were predominantly low grade; grade 3 or higher CRS occurred in 5% of patients who received ide-cel and 1.1% of those who received cilta-cel, and severe neurologic toxicity was infrequent with both agents.

“Randomized phase 3 evidence demonstrates a large and consistent PFS benefit with BCMA-directed CAR-T therapy compared with active standard regimens in [relapsed/refractory multiple myeloma], with a pooled 55% reduction in progression or death and no observed statistical heterogeneity,” lead author Vasu Malhotra, DO, a resident in Internal Medicine and General Internal Medicine at Lakeland Regional Health Medical Center, wrote with coauthors in the poster.³ “These findings support moving BCMA-directed CAR-T therapy earlier in the treatment course of appropriately selected patients with [relapsed/refractory multiple myeloma] rather than reserving cellular therapy exclusively for heavily pretreated disease.”

References

1. Usmani SZ, Facon T, Hungria V, et al. Daratumumab plus bortezomib, lenalidomide, and dexamethasone (D-VRd) in patients with newly diagnosed multiple myeloma: final analysis of transplant-ineligible (TIE) patients in the phase 3 CEPHEUS study. Presented at: Society of Hematologic Oncology (SOHO) 2026 Annual Meeting; September 9-12, 2026; Houston, TX. Abstract MM-338.
2. Baljevic M, Moore DC, Lee HC, et al. Navigating bispecifics outpatient step-up dosing: a roadmap to help improve safety and access in the real-world (NORTHSTAR). Presented at: SOHO 2026 Annual Meeting; September 9-12, 2026; Houston, TX. Abstract MM-548.
3. Malhotra V, Patel SG, Shain KH. Phase III randomized evidence for BCMA-directed CAR T-cell therapy versus standard regimens in relapsed/refractory multiple myeloma: a systematic review and meta-analysis. Presented at: SOHO 2026 Annual Meeting; September 9-12, 2026; Houston, TX. Abstract MM-1517.