ASH 2025: Which Presentations Will Move the Multiple Myeloma Needle?

One presentation that Al-Ola A. Abdallah, MD, identified was related to the phase 3 COBRA trial (NCT03729804), in which investigators evaluated carfilzomib in combination with lenalidomide and dexamethasone (KRd) compared with bortezomib plus lenalidomide and dexamethasone (VRd) for those with newly diagnosed multiple myeloma.

It’s that time of the year again; the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition is almost here. Experts across different hematologic malignancy specialties will convene in Orlando, Florida, to unveil the latest developments in novel treatment modalities, translational research, and other key discoveries that may inform clinical practice across various blood cancer indications.

In a series of posts on X, ONCOLOGY® editorial advisory board member Al-Ola A. Abdallah, MD, highlighted a series of multiple myeloma abstracts that may indicate notable advances in the therapeutic landscape. Abdallah is an associate professor of medicine and the director of the Plasma Cell Disorder Clinic in the Division of Hematologic Malignancies and Cellular Therapeutics at the University of Kansas Medical Center.

From phase 3 trial updates to sessions exploring trispecific antibodies and other investigational compounds, here are some of the abstracts that may shake up multiple myeloma care.

Abstract 99: Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide and dexamethasone (VRd) in patients with newly diagnosed multiple myeloma (NDMM) – interim results from the randomized phase III COBRA trial.1

Presentation: December 6, 10:00 – 10:15 AM EST by Dominik Dytfeld, MD, PhD

One presentation that Abdallah identified was related to the phase 3 COBRA trial (NCT03729804), in which investigators evaluated carfilzomib (Kyprolis) in combination with lenalidomide (Revlimid) and dexamethasone (KRd) compared with bortezomib (Velcade) plus lenalidomide and dexamethasone (VRd) for those with newly diagnosed multiple myeloma (NDMM).

“VRd is the current frontline standard. KRd has shown strong activity, but previous head-to-heads (e.g., ENDURANCE [NCT01863550]) didn’t show progression-free survival [PFS] benefit,” Abdallah wrote on X.2 “COBRA revisits this across all [patients with] NDMM, regardless of transplant eligibility or cytogenetics.”

According to the abstract, efficacy improved with KRd vs VRd in this NDMM population; the safety profiles of the regimens were comparable with previous reports.1 Findings from this trial may support further investigation of KRd-based induction regimens.

LBA6: Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or Bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): Results of majestec-3.3

Presentation: December 9, 8:45 – 9:00 AM EST by María-Victoria Mateos, MD, PhD

Another noteworthy presentation will unveil detailed results from the phase 3 MajesTEC-3 study (NCT05083169) evaluating subcutaneous daratumumab and hyaluronidase-fihj (Darzalex Faspro) plus teclistamab-cqyv (Tecvayli) vs standard-of-care therapy among patients with relapsed/refractory multiple myeloma.

According to Abdallah, “attrition rises” while “response durability falls” with each line of therapy in the relapsed/refractory setting, thus necessitating the early introduction of immunotherapies.4 He described how, based on the MajesTEC-3 trial, the immune-permissive microenvironment created by daratumumab may effectively synergize with the T-cell redirection capabilities of teclistamab.

In October 2025, topline results showed that the teclistamab combination significantly improved different survival outcomes vs standard therapy in the MajesTEC-3 study.5 After approximately 3 years of follow-up, investigators noted showed statistically significant improvements in PFS and overall survival (OS) among patients who received the experimental combination vs those who were treated with daratumumab plus pomalidomide (Pomalyst) and dexamethasone (DPd) or bortezomib (Velcade) and dexamethasone (DVd).

Abstract 100: Safety and efficacy of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma: Results from the phase 1b MagnetisMM-30 trial.6

Presentation: December 6, 10:15– 10:30 AM by Attaya Suvannasankha, MD

One presentation will shed light on early findings from the phase 1b MagnetisMM-30 trial (NCT06215118), which explored the use of elranatamab-bcmm (Elrexfio) plus iberdomide, an investigational CELMoD, for patients with relapsed/refractory multiple myeloma.

In his breakdown of this study, Abdallah stated that elranatamab has produced “deep responses in prior trials,” while iberdomide has shown “enhanced immunomodulatory and antimyeloma activity.”7 He noted that these agents may collectively offer a “potent, fully off-the-shelf combination” in the relapsed/refractory setting.

Early findings shared in the presentation abstract described a favorable safety profile and encouraging efficacy with the elranatamab-based regimen in this trial population.6

Abstract 4042: Updated efficacy and safety results of JNJ-5322, a novel, next-generation BCMA×GPRC5D×CD3 trispecific antibody, in patients with relapsed/refractory multiple myeloma.8

Presentation: December 7, 6:00 – 8:00 PM EST by Amrita Krishnan, MD

Regarding notable poster sessions, Abdallah emphasized one presentation detailing additional findings associated with the use of the trispecific antibody JNJ-5322 (JNJ-79635322) among patients with relapsed/refractory multiple myeloma in a first-in-human phase 1 trial (NCT05652335). With an ability to target BCMA, GPRC5D, and CD3 while improving binding, overcoming clonal heterogeneity, and reducing antigen escape, Abdallah stated that JNJ-5322 may be built “for deep, durable responses.”9

Investigators previously highlighted a manageable safety profile and responses with JNJ-5322 based on a presentation of earlier findings from the phase 1 trial at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.10

References

1. Dytfield D, Kubicki T, Tyczynska A, et al. Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide and dexamethasone (VRd) in patients with newly diagnosed multiple myeloma (NDMM) – interim results from the randomized phase III COBRA trial. To be presented at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition; December 6-9, 2025; Orlando, FL. Abstract 99.
2. @Abdallah81MD. 2/🧪 Why it matters: VRd is the current frontline standard. KRd has shown strong activity, but previous head-to-heads (e.g., ENDURANCE) didn’t show PFS benefit. COBRA revisits this across all NDMM patients, regardless of transplant eligibility or cytogenetics. #USMIRC @USMIRCNEWS #myeloma #MedEd #MedTwitter @OncoAlert @MedwatchKate @Larvol @US_HMC #سرطان_الدم #المايلوما. November 22, 2025. Accessed December 2, 2025. https://x.com/Abdallah81MD/status/1992098593499439519?s=20
3. Mateos M-V, Bahlis N, Perrot A, et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or Bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): results of majestec-3. To be presented at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition; December 6-9, 2025; Orlando, FL. Abstract LBA6.
4. @Abdallah81MD. 2/ 🧬 Why this matters: In RRMM, attrition rises & response durability falls with each LOT. Early introduction of effective immunotherapies is crucial. Dara creates an immune-permissive microenvironment → synergistic with Tec’s T-cell redirection. 💥 #mmsm #MedEd #myeloma #MedTwitter #USMIRC @USMIRCNEWS @US_HMC @OncoAlert @Larvol @MedwatchKate. November 24, 2025. Accessed December 2, 2025. https://x.com/Abdallah81MD/status/1993033537671381376?s=20
5. TECVAYLI plus DARZALEX FASPRO combination regimen significantly improves progression-free survival and overall survival versus standard of care. News release. Johnson & Johnson. October 16, 2025. Accessed December 2, 2025. https://tinyurl.com/4vd4uss9
6. Suvannasankha A, Kaufman J, Badros A, et al. Safety and efficacy of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma: Results from the phase 1b MagnetisMM-30 trial. To be presented at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition; December 6-9, 2025; Orlando, FL. Abstract 100.
7. @Abdallah81MD. 2/💡 Why this matters ELRA is a BCMA×CD3 bispecific with deep responses in prior trials. IBER is a next-gen CELMoD with enhanced immunomodulatory & antimyeloma activity. Together, they may offer a potent, fully off-the-shelf combination for RRMM #mmsm #myeloma #MedEd #MedTwitter #USMIRC @USMIRCNEWS @US_HMC @oncodaily @Larvol @MedwatchKate #سرطان_الدم #المايلوما. November 18, 2025. Accessed December 2, 2025. https://x.com/Abdallah81MD/status/1990991284614414341?s=20
8. Krishnan A, Kaiser M, Popat R, et al. Updated efficacy and safety results of JNJ-5322, a novel, next-generation BCMA×GPRC5D×CD3 trispecific antibody, in patients with relapsed/refractory multiple myeloma. To be presented at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition; December 6-9, 2025; Orlando, FL. Abstract 4042.
9. @Abdallah81MD. 2/🔬 What is JNJ-5322? A novel trispecific antibody targeting BCMA + GPRC5D + CD3 — designed to improve binding, overcome clonal heterogeneity, & reduce antigen escape. Built for deep, durable responses. 💥 #mmsm #myeloma #MedEd #MedTwitter @US_HMC @USMIRCNEWS @OncoAlert @MedwatchKate @Larvol #سرطان_الدم #المايلوما. November 22, 2025. Accessed December 2, 2025. https://x.com/Abdallah81MD/status/1992401263187611970?s=20
10. van de Donk NW, Vega G, Perrot A, et al. First-in-human study of JNJ-79635322 (JNJ-5322), a novel, next-generation trispecific antibody (TsAb), in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial phase 1 results. J Clin Oncol. 2025;43(suppl 16):7505. doi:10.1200/JCO.2025.43.16_suppl.7505