Early-Line Immunotherapy Challenges the Role of Transplant in Multiple Myeloma

The treatment landscape for multiple myeloma (MM) continues to evolve as novel immunotherapies move earlier in the disease course, raising questions about the long-standing role of high-dose chemotherapy and autologous stem cell transplant. Results from the phase 2 ImmunoPLANT clinical trial (NCT06376526)¹ presented at the 2025 American Society of Hematology (ASH) Annual Meeting indicate that a monoclonal antibody combination involving linvoseltamab (Lynozyfic; Regeneron) may yield significant responses in patients who have traditionally qualified for transplant procedures.²

Researchers at the University of Miami Miller School of Medicine found that patients enrolled in the trial achieved significant tumor reduction after contemporary induction treatment. A number of patients even attained the depletion of minimal residual disease. This highlights the increasing role for immunotherapy-directed strategies in first-line treatment for MM.²

ImmunoPLANT Trial Design and Rationale

The ImmunoPLANT phase 2 trial aimed to determine if patients who were newly diagnosed with MM and were highly responsive to initial therapy could bypass high-dose chemotherapy and stem cell transplant (SCT). The patients underwent current-day therapy regimens, followed by the bispecific antibody linvoseltamab, which targets BCMA and is designed to engage T cells for targeted killing of myeloma plasma cells.²

According to investigators, this reflects a broader shift towards response-adapted therapy, in which treatment intensity is tailored based on depth of response rather than automatically escalating to a transplant. Historically, transplant has been considered a standard of care for eligible patients, despite a well-documented toxicity burden with prolonged recovery.³

Deep Responses Without High-Dose Chemotherapy

Investigators reported that approximately 90% of tumor burden was eliminated in patients receiving the immunotherapy-based approach. Ajai Chari Kazandjian, MD, highlighted the significance of this response in the context of historical treatment paradigms.

“These patients received modern and effective, up-front treatment that eliminated 90% of their tumor,” said Dr. Kazandjian. “Usually, patients like these would receive high-dose chemotherapy and transplant. Instead, we give them a treatment with the drug linvoseltamab.”²

The capacity to produce such profound responses without resorting to a melphalan transplant dose has great significance in consideration of risks of transplantation in the long term, like secondary malignancies, cytopenias, infections, and quality of life issues.^3,4

Minimal Residual Disease and Long-Term Implications

Ola Landgren, MD, PhD, professor and chief of the Myeloma Division at the Miller School, described the trial’s early outcomes as highly encouraging, particularly the disappearance of lingering myeloma cells detectable by sensitive measurable residual disease (MRD) assays.

Dr. Landgren called the results so far “extremely impressive” and noted that clearance of residual disease is strongly associated with improved progression-free and overall survival in multiple myeloma.^2,5

“Based on my experience, I would predict that after having such a good response after such a short time, the disease most likely could stay away for many years,” he said. “Could it never come back in some patients? I would say it’s possible.”²

MRD negativity is rapidly proving to be an important prognostic factor for patients with MM, with increasing interest in using it as an endpoint for clinical research.² The potential for achieving MRD negativity without undergoing an autotransplant may pave the way for targeting lower-level treatment.

Reconsidering Transplant in the Modern Era

Despite its historical role, autologous stem cell transplant remains a physically demanding intervention. Dr. Landgren emphasized the contrast between transplant and emerging immunotherapies.²

“It’s a quite brutal therapy, which was first introduced in the U.K. in 1983,” he said, referring to high-dose chemotherapy and transplant.²

As immunotherapeutic regimens begin to express deeper and more profound levels of response earlier, there is increasing debate regarding whether transplant should remain mandatory in all eligible patients or be reserved for relapse situations.^4,5

Although experts suggest that a deeper follow-up is required before modifying clinical practice guidelines, evidence emerging in the immunoPLANT study contributes to a growing body of evidence supporting transplant-sparing approaches in select patients.

Implications for Pharmacists and Clinical Practice

From a pharmaceutical perspective, these results confirm the growing role of immunotherapy in MM treatment and underscore the importance of understanding new mechanisms of action, toxicities, and supportive requirements. Bispecific antibodies, including linvoseltamab, require close follow-up for cytokine release syndrome, infections, and hematologic toxicities, all of which are important areas where pharmacists play a significant role.

Dr. Landgren emphasized the aspirational nature of the trial’s goals. “It’s a bold claim, but we need to aim for the stars to move the field forward,” he said. “That is what we are trying to do.”²

As data mature, immunotherapy-driven strategies may redefine frontline myeloma care, offering patients effective disease control with fewer long-term consequences and reshaping how pharmacists support therapy selection and monitoring.

REFERENCES

1. NCT06376526.IMMUNOPLANT for Newly Diagnosed Multiple Myeloma (IMMUNOPLANT). Clinicaltrials.gov. Updated August 14, 2025 . Accessed January 20, 2026. https://clinicaltrials.gov/study/NCT06376526

2. Antibody Therapy Eradicates Traces of Multiple Myeloma in Preliminary Trial. Miller School of Medicine. Published December 6, 2025. Accessed January 20, 2026. https://news.med.miami.edu/ash-2025-immunoplant-phase-2-trial/

3. Rocchi S, Zannetti BA, Marconi G, Lanza F. Multiple Myeloma: The Role of Autologous Stem Cell Transplantation in the Era of Immunotherapy. Cells. 2024;13(10):853. Published 2024 May 16. doi:10.3390/cells13100853

4. Devarakonda S, Efebera Y, Sharma N. Role of Stem Cell Transplantation in Multiple Myeloma. Cancers (Basel). 2021;13(4):863. Published 2021 Feb 18. doi:10.3390/cancers13040863

5. Banerjee R., Klumpp E. Video: Bispecific Antibodies in Myeloma with Dr. Rahul Banerjee- Highlights from ASH 2025. Published December 15, 2025. Accessed January 20, 2026. https://www.cancertherapyadvisor.com/features/bispecific-antibodies-in-multiple-myeloma-ash-2025/