Relapsed/Refractory Multiple Myeloma Clinical Trials — 2026 Pipeline Tracker

Phase 3 recruiting RRMM trials (2026)

The table below covers major Phase 3 and Phase 2/3 randomized studies currently enrolling patients with relapsed or refractory multiple myeloma. Data sourced from ClinicalTrials.gov and updated daily by DataLookout.

NCT ID	Trial / Drug	Regimen vs. Comparator	Sponsor	Phase
NCT05519085	MEZIVd — Mezigdomide + bortezomib + dexamethasone	MEZIVd vs. standard-of-care backbone in ≥1 prior line RRMM	Celgene / BMS	Phase 3
NCT06152575	MagnetisMM-32 — Elranatamab + daratumumab	ElraDara vs. standard in lenalidomide-exposed RRMM (1–3 prior lines)	Pfizer	Phase 3
NCT05623020	MagnetisMM — Elranatamab + daratumumab + pomalidomide	Elra + Dara + Pom vs. standard triplet in RRMM	Pfizer	Phase 3
NCT07222761	Linvoseltamab vs. Linvoseltamab + carfilzomib	Linvoseltamab monotherapy vs. linvo + carfilzomib combination in RRMM	Regeneron	Phase 3
NCT07258511	JNJ-79635322 (FcRH5 bispecific)	JNJ-79635322 vs. investigator-choice anti-BCMA standard in heavily pretreated RRMM	J&J / Janssen	Phase 3
NCT06615479	BMS-986393 (CEA-CAR-T / next-gen BCMA CAR-T)	BMS-986393 vs. standard care in RRMM (post ≥2 prior lines)	Juno / BMS	Phase 3
NCT05438043	Daratumumab combination regimen	Daratumumab-based combination vs. comparator in RRMM	J&J / Janssen	Phase 3
NCT07095452	AbbVie BCMA-targeting regimen	AbbVie investigational BCMA agent ± backbone vs. standard in RRMM	AbbVie	Phase 2/3

Table reflects recruiting status as of March 2026. Verify current enrollment status at ClinicalTrials.gov before making clinical or investment decisions.

Understanding relapsed/refractory multiple myeloma

Relapsed/refractory multiple myeloma (RRMM) is the dominant clinical context for myeloma drug development. The term covers two overlapping scenarios: disease that has relapsed — meaning it returned after a period of remission — and disease that is refractory, meaning it failed to respond adequately to a given therapy or progressed within 60 days of the last dose. In practice, most patients in later lines meet both definitions simultaneously.

The epidemiological reality is stark: more than 90% of myeloma patients will eventually develop RRMM. Multiple myeloma is currently incurable with standard therapy. Even patients who achieve a complete response after frontline treatment — daratumumab, bortezomib, lenalidomide, and dexamethasone (Dara-VRd) or similar induction — will almost universally relapse. As each subsequent line produces progressively shorter remissions, RRMM represents both the largest unmet clinical need and the most commercially important therapeutic setting in myeloma.

Current standard of care in RRMM

The landscape of approved RRMM therapies has expanded dramatically since 2020. Key regimens include:

• Daratumumab + pomalidomide + dexamethasone (DPd): Anti-CD38 antibody triplet; approved in ≥1 prior line, highly active in lenalidomide-refractory disease
• Carfilzomib combinations (KPd, KRd): Carfilzomib remains a backbone in early relapse, particularly for bortezomib-sensitive or bortezomib-refractory patients who have not received a second-generation PI
• Isatuximab + pomalidomide + dexamethasone (IsaPd): Second anti-CD38 approved in ≥2 prior lines; also active in combinations with carfilzomib (IsaKd)
• Teclistamab (Tecvayli): First approved BCMA bispecific antibody; subcutaneous, weekly dosing after step-up; approved in ≥4 prior lines
• Elranatamab (Elrexfio): Second approved BCMA bispecific; similar mechanism, subcutaneous; approved in ≥4 prior lines
• Talquetamab (Talvey): First approved GPRC5D bispecific; active post-BCMA; distinct mechanism and toxicity profile
• Ide-cel (Abecma) and cilta-cel (Carvykti): Approved autologous BCMA CAR-T therapies for ≥4 and ≥1 prior lines respectively
• Selinexor (Xpovio): XPO1 nuclear export inhibitor; used as a bridging agent and in post-CAR-T or post-bispecific settings

The bispecific antibody revolution in RRMM

The approval of teclistamab in September 2022 marked a turning point in RRMM therapeutics. Bispecific T-cell engagers simultaneously bind BCMA on myeloma cells and CD3 on T cells, redirecting cytotoxic T-cell killing without requiring ex-vivo T-cell manipulation. Three BCMA bispecifics are now approved or in late-stage development: teclistamab (Tecvayli, J&J), elranatamab (Elrexfio, Pfizer), and linvoseltamab (Regeneron REGN5458, in rolling BLA submission).

The 2026 pipeline represents the second generation of bispecific development: moving these agents earlier in the treatment sequence, combining them with established backbones, and testing them head-to-head or in combination with proteasome inhibitors and anti-CD38 antibodies. Pfizer's MagnetisMM-32 program (NCT06152575) is the clearest expression of this strategy — combining elranatamab with daratumumab specifically in lenalidomide-exposed patients at first or second relapse, targeting the large and growing daratumumab-naive RRMM population.

A key clinical advantage of BCMA bispecifics over CAR-T is subcutaneous administration and off-the-shelf availability. Elranatamab and teclistamab are both delivered subcutaneously following a step-up dosing schedule to mitigate cytokine release syndrome (CRS), without apheresis, manufacturing wait, or specialized treatment center infrastructure. This makes them broadly deployable across community oncology settings — a significant commercial advantage over CAR-T.

Linvoseltamab (Regeneron REGN5458)

Linvoseltamab is Regeneron's BCMA × CD3 bispecific antibody, with a BLA under rolling review by the FDA as of early 2026. Phase 2 data (LINKER-MM1) demonstrated a 71% overall response rate in heavily pretreated RRMM, with deep responses including complete responses in a substantial subset. Regeneron's Phase 3 strategy — reflected in NCT07222761 — tests whether adding carfilzomib to linvoseltamab can deepen and extend responses, building the bispecific into standard triplet frameworks. This head-to-head design (monotherapy vs. combination) will define the future labeling strategy and commercial positioning for linvoseltamab.

CELMoDs: next-generation cereblon modulators

Cereblon E3 Ligase Modulatory Drugs (CELMoDs) are the next chapter of the IMiD story. Thalidomide, lenalidomide, and pomalidomide all act by binding cereblon and inducing degradation of the Ikaros and Aiolos transcription factors — proteins essential for myeloma cell survival. But first-generation IMiDs have incomplete activity against these targets and are subject to resistance driven by IKZF1/3 mutations and cereblon downregulation.

CELMoDs — specifically mezigdomide (CC-92480) and iberdomide (CC-220) — bind cereblon with significantly higher affinity and produce more complete substrate degradation. In preclinical models, mezigdomide retains activity in lenalidomide-refractory and pomalidomide-refractory cell lines. Early clinical data from the CC-92480-MM-001 study showed an overall response rate of approximately 40% in patients refractory to a median of 5 prior lines including prior IMiD therapy.

The MEZIVd trial (NCT05519085, Celgene/BMS) represents the pivotal Phase 3 moment for mezigdomide: testing it in combination with bortezomib and dexamethasone (VD) — a well-established backbone — against a standard-of-care comparator in RRMM patients with 1–3 prior lines. A positive result would position mezigdomide as a new standard in the post-lenalidomide second-line setting, displacing pomalidomide as the IMiD of choice for lenalidomide-refractory patients.

CAR-T cell therapy in RRMM: next-generation programs

Idecabtagene vicleucel (Abecma, ide-cel) and ciltacabtagene autoleucel (Carvykti, cilta-cel) established BCMA-targeted CAR-T as a standard option in RRMM. Cilta-cel's CARTITUDE-4 data were particularly compelling, demonstrating superiority over standard of care in patients with 1–3 prior lines — accelerating its use into earlier relapse settings. But manufacturing constraints, apheresis requirements, and the competitive threat from BCMA bispecifics have opened the door to next-generation CAR-T programs.

BMS-986393 — next-generation BCMA CAR-T

BMS-986393 (developed by Juno/BMS) is an optimized BCMA CAR-T construct moving into Phase 3 via NCT06615479. While technical details of its specific modifications are not fully disclosed, next-generation CAR-T programs generally incorporate improvements such as: fully-human or optimized scFv domains to reduce immunogenicity, 4-1BB co-stimulatory domains for persistence, enriched memory T-cell subsets (TSCM or TCM), and manufacturing processes that reduce the proportion of exhausted T cells. Phase 3 testing against standard care in ≥2 prior line RRMM positions BMS-986393 as a potential successor to ide-cel, with potentially improved efficacy, safety, or manufacturing reliability.

JNJ-79635322 — novel target bispecific or CAR-T

JNJ-79635322 (J&J/Janssen, NCT07258511) is one of the most strategically significant trials in the 2026 RRMM pipeline. This Phase 3 trial pits JNJ-79635322 — which may target FcRH5 or an alternative BCMA epitope — head-to-head against investigator-choice anti-BCMA standard therapy. The significance: if JNJ-79635322 targets a non-overlapping antigen like FcRH5 (the same target as cevostamab), it addresses one of the most pressing unmet needs in RRMM — what to give patients after BCMA therapy has failed. A positive head-to-head result against anti-BCMA standard would be practice-defining for the post-BCMA treatment sequence.

Treatment sequencing: the critical clinical challenge

The proliferation of approved therapies in RRMM has created a new clinical and competitive challenge: sequencing. With BCMA-targeting agents now used in multiple lines, clinicians and drug developers must address what comes next when BCMA therapy fails — either through antigen loss, T-cell exhaustion, or other resistance mechanisms.

Current strategies for post-BCMA RRMM include:

• GPRC5D targeting: Talquetamab (Talvey, J&J) — approved bispecific with a distinct antigen; active post-BCMA and post-CAR-T in Phase 2 data from MonumenTAL-1
• FcRH5 targeting: Cevostamab (Roche) in Phase 2; JNJ-79635322 now in Phase 3 — targets a different surface antigen expressed on myeloma cells
• CD38 rechallenge: Limited data, but some patients who had prior daratumumab have responded to isatuximab or re-challenge after a treatment-free interval
• Selinexor (Xpovio): XPO1 inhibitor active as a bridging option or in patients who have exhausted immunotherapy options; approved as Xpovio + dexamethasone and in the XVd regimen

Eligibility criteria in current Phase 3 trials reflect these sequencing realities. MEZIVd (NCT05519085) specifically targets patients earlier in the relapse sequence (1–3 prior lines), while JNJ-79635322's Phase 3 targets later-line patients already exposed to anti-BCMA therapy. MagnetisMM-32 (NCT06152575) is specifically designed for lenalidomide-exposed (rather than lenalidomide-refractory) patients — recognizing that lenalidomide-naive patients have different biology and response characteristics than those who have failed lenalidomide outright.

Key eligibility variables in RRMM trials

• Prior lines: 2nd-line (≥1 prior) vs. 3rd-line+ (≥2 prior) vs. penta-refractory (≥5 prior) — determines competitive landscape and enrollment difficulty
• Lenalidomide-refractory vs. lenalidomide-exposed: Critical distinction — refractory implies IMiD resistance mechanism; exposed implies prior use but not necessarily resistance
• Triple-class refractory status: Refractory to PI + IMiD + anti-CD38; standard eligibility gate for later-line trials; most approved bispecifics were tested in this population
• Prior BCMA therapy: Increasingly important eligibility criterion as bispecifics and CAR-T become standard; post-BCMA trials require explicit prior BCMA exposure
• Cytogenetic risk: High-risk features (del17p, t(4;14), t(14;16)) correlate with aggressive relapse biology; trials increasingly stratify by cytogenetic risk at randomization

Frequently asked questions about RRMM clinical trials

What is relapsed/refractory multiple myeloma?

Relapsed/refractory multiple myeloma (RRMM) is myeloma that has either come back (relapsed) after a period of response to prior therapy, or has never responded adequately to treatment (refractory). More than 90% of myeloma patients will eventually develop RRMM. The disease is considered refractory when it progresses during active therapy or within 60 days of the last dose. Each subsequent line of therapy typically produces shorter remissions, making RRMM one of the most active areas of clinical drug development in oncology.

What are the current treatment options for RRMM after 3 prior lines?

For triple-class refractory RRMM (refractory to a proteasome inhibitor, an IMiD, and an anti-CD38 antibody) after 3+ prior lines, approved options include: teclistamab (Tecvayli), elranatamab (Elrexfio), and linvoseltamab — BCMA bispecific antibodies — as well as talquetamab (Talvey) targeting GPRC5D, ide-cel (Abecma) and cilta-cel (Carvykti) as BCMA CAR-T therapies, selinexor (Xpovio), and belantamab mafodotin (Blenrep, re-approved 2023). Treatment sequencing after prior BCMA therapy remains an active area of research, with FcRH5-targeting agents and GPRC5D-directed therapy emerging as post-BCMA options.

What is the difference between BCMA bispecifics and CAR-T in RRMM?

Both target BCMA on myeloma cells but differ in administration, mechanism, and accessibility. BCMA bispecifics (teclistamab, elranatamab, linvoseltamab) are off-the-shelf drugs given by subcutaneous injection on an ongoing basis — no manufacturing wait, broadly accessible. BCMA CAR-T therapies (ide-cel, cilta-cel) require harvesting the patient's own T cells, a 4–6 week manufacturing process, and a single infusion — with potentially deeper and more durable responses in eligible patients but significant logistical complexity. A key open question in 2026: does prior BCMA bispecific exposure impair subsequent CAR-T efficacy? Emerging data suggest partial cross-resistance, favoring early CAR-T in eligible patients.

What is a CELMoD and how does it differ from thalidomide, lenalidomide, and pomalidomide?

CELMoDs (Cereblon E3 Ligase Modulatory Drugs) are the next generation of cereblon-targeting agents that degrade the Ikaros and Aiolos transcription factors critical for myeloma cell survival. Unlike first-generation IMiDs, mezigdomide and iberdomide bind cereblon with greater affinity and produce more complete substrate degradation — resulting in deeper anti-myeloma activity even in IMiD-refractory disease. Mezigdomide (CC-92480) is the furthest advanced, now in Phase 3 via the MEZIVd trial testing it in combination with bortezomib and dexamethasone.

How can I get email alerts for new RRMM clinical trials?

DataLookout monitors ClinicalTrials.gov daily and sends email digests when new or updated RRMM trials are registered. Sign up free at datalookout.com — set your topic to "multiple myeloma relapsed" and receive daily or weekly alerts filtered by phase, sponsor type, and recruiting status. The free plan covers 1 tracker with weekly digests; paid plans add daily delivery and multiple concurrent trackers.