Sergio A. Giralt, MD, deputy division head, Division of Hematologic Malignancies, Melvin Berlin Family Chair in Multiple Myeloma, Memorial Sloan Kettering Cancer Center, discusses the rationale for investigating idecabtagene vicleucel (ide-cel; Abecma) vs standard-of-care regimens in patients with triple-class exposed relapsed/refractory multiple myeloma in the phase 3 Karmma-3 trial (NCT03651128).

The treatment landscape in multiple myeloma has evolved dramatically in recent years, Giralt begins. With the use of anti-CD38 monoclonal antibodies in combination with proteasome inhibitors and immunomodulatory drugs as frontline treatment or salvage therapy, patients with multiple myeloma are now being exposed to the most active agents in early settings, Giralt says.

ide-cel for patients with relapsed/refractory multiple myeloma

 after 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Additionally, the CAR T-cell therapy 

ciltacabtagene autoleucel (cilta-cel; Carvykti)

 in February 2022 for adult patients with relapsed/refractory multiple myeloma following 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Despite the availability of these CAR T-cell therapies in later-line settings, many patients with multiple myeloma are triple-class exposed and become refractory to those other 3 major drug types within the second or third line of treatment, Giralt emphasizes.

Karmma-3 trial was designed to evaluate ide-cel in patients with multiple myeloma who were triple-class exposed and received 2 to 4 prior lines of treatment, Giralt says. This trial was essential to help understand if ide-cel should be used earlier in the course of the treatment journey for patients who are triple-class exposed and refractory to their last treatment, Giralt concludes.

Videos

Sergio A. Giralt, MD, discusses the rationale for investigating idecabtagene vicleucel vs standard-of-care regimens in patients with triple-class exposed relapsed/refractory multiple myeloma in the phase 3 Karmma-3 trial.

Dr. Giralt on the Rationale of the Karmma-3 trial of Ide-cel in R/R Myeloma

Sergio A. Giralt, MD, deputy division head, Division of Hematologic Malignancies, Melvin Berlin Family Chair in Multiple Myeloma, Memorial Sloan Kettering Cancer Center, discusses the potential utility of omidubicel in hematologic malignancies. 

The results of a randomized phase 3 clinical trial (NCT01597778) demonstrated similar 2-year progression-free survival rates with double unrelated umbilical cord blood transplant vs human leukocyte antigen (HLA)–haploidentical bone marrow transplant in patients with chemotherapy-sensitive lymphoma or acute leukemia in remission. 

In recent years, the number of cord blood transplants has decreased likely because the procedure is associated with slow engraftment and high resource utilization, says Giralt. However, during the 47th Annual Meeting of the EBMT, findings from a phase 3 trial of omidubicel, a cryopreserved cellular product derived from a single umbilical cord blood unit and expanded 

, vs standard umbilical cord blood transplant (UBCT) in patients with high-risk hematologic malignancies following myeloablation were presented virtually. The results demonstrated improved CD34-positive cell expansion and quicker time to neutrophil engraftment with omidubicel vs UBCT. 

As such, clinical trials could explore cord blood transplant with omidubicel to benefit patients who do not have a related or unrelated donor available, concludes Giralt. 

Sergio A. Giralt, MD, discusses the potential utility of omidubicel in hematologic malignancies.  



Dr. Giralt on the Potential Utility of Omidubicel in Hematologic Malignancies 

Sergio A. Giralt, MD, deputy division head, Division of Hematologic Malignancies, Melvin Berlin Family Chair in Multiple Myeloma, Memorial Sloan Kettering Cancer Center, discusses the results of a phase 3 trial (NCT02730299) comparing omidubicel with standard umbilical cord blood transplant (UCBT) in hematologic malignancies.

During the 47th Annual Meeting of the EBMT, the results of a phase 3 trial of omidubicel, a cryopreserved cellular product derived from a single umbilical cord blood unit and expanded 

, vs standard UCBT in patients with high-risk hematologic malignancies following myeloablation were presented virtually. The findings demonstrated a 124-fold improvement in CD34-positive cell expansion with omidubicel vs UCBT at 9 x 10

 cells/kg, respectively. The median time to neutrophil engraftment was 12 days with omidubicel vs 22 days with UCBT. Non-relapse mortality at 180 days after treatment, 1-year relapse rate, and 1-year probability of overall survival did not differ significantly between arms but favored omidubicel. 

Additionally, patients who received omidubicel had a higher incidence of 42-day platelet engraftment, a lower incidence of grade 2 or 3 bacterial or invasive fungal infection, and spent less time hospitalized within 100 days after transplant compared with standard UBCT.

Comparative trials of omidubicel vs haploidentical transplant with post-transplant cyclophosphamide could shed additional light on the utility of omidubicel in this patient population, concludes Giralt. 

Sergio A. Giralt, MD, discusses the results of a phase 3 trial comparing omidubicel with standard umbilical cord blood transplant in hematologic malignancies.  



Dr. Giralt on Omidubicel Vs Standard Umbilical Cord Blood Transplant in Hematologic Malignancies 

Sergio A. Giralt, MD, professor of medicine at Weill Cornell Medical College, and chief, Adult Bone Marrow Transplant Service, Melvin Berlin Family Chair in Multiple Myeloma, at Memorial Sloan Kettering Cancer Center, discusses the current frontline standard of care for patients with multiple myeloma.

The current frontline standard of care in multiple myeloma is bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd), explains Giralt. In patients with renal failure or dysfunction, the combination of lenalidomide, cyclophosphamide, and dexamethasone is also commonly used, according to Giralt.

Randomized trials have shown that 3-drug regimens are better than 2-drug regimens for both transplant-eligible and -ineligible patients. The SWOG S0777 trial showed that VRd had an improved survival compared with lenalidomide and dexamethasone alone, concludes Giralt.

Sergio A. Giralt, MD, discusses the current frontline standard of care for patients with multiple myeloma.

Dr. Giralt on Current Standard of Care for Newly Diagnosed Multiple Myeloma

Sergio A. Giralt, MD, professor of medicine at Weill Cornell Medical College, and chief, Adult Bone Marrow Transplant Service, Melvin Berlin Family Chair in Multiple Myeloma, at Memorial Sloan Kettering Cancer Center, discusses methods of evaluating measurable residual disease (MRD) in multiple myeloma.

MRD, commonly referred to as minimal residual disease, is somewhat of a misnomer, says Giralt, as it implies that the disease has been eradicated. However, that is not always the case. As such, measurable residual disease might be a more appropriate term, he suggests. Currently, 2 assays are available to measure MRD, including next-generation sequencing and flow cytometry. These assays have a sensitivity that ranges from 1 in 100,000,000 to 1 in 1,000,000,000 myeloma cells in the bone marrow.

MRD negativity has been shown to be a positive prognostic outcome. However, it is unknown whether converting an MRD-positive patient to an MRD-negative patient has any impact on survival, and what the ideal timing to measure MRD is, says Giralt. As such, MRD is not currently being used to guide treatment decisions in multiple myeloma, concludes Giralt.

Dr. Giralt on Evaluating MRD in Multiple Myeloma

Sergio A. Giralt, MD, professor of medicine at Weill Cornell Medical College, and chief, Adult Bone Marrow Transplant Service, Melvin Berlin Family Chair in Multiple Myeloma, at Memorial Sloan Kettering Cancer Center, discusses transplant eligibility criteria in multiple myeloma.

A patient’s performance status and comorbidities should be evaluated to determine whether they are a candidate for transplant, says Giralt. If eligible, patients over the age of 75 may also undergo a geriatric assessment to determine what type of transplant they are best suited to receive. Age is one factor that should not impact the decision, adds Giralt.

There is a belief that patients in renal failure on dialysis should not undergo transplant. However, studies have demonstrated that patients on dialysis can receive high-dose melphalan safely, enabling them to undergo transplant. Furthermore, some patients are able to subsequently recover kidney function and come off dialysis, concludes Giralt.

Dr. Giralt on Transplant Eligibility Criteria in Multiple Myeloma

Sergio A. Giralt, MD, professor of medicine at Weill Cornell Medical College, the Melvin Berlin Family Chair in Multiple Myeloma, and chief attending of adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center, discusses the role of allogeneic hematopoietic cell therapy (HCT) in patients with multiple myeloma.

Giralt says this is a valid option for patients and should not be dismissed. This option has been available to patients for over 2 decades, though experts are aware that the results aren’t exactly what they hope. A number of clinical trials are exploring allogeneic HCT to improve the outcomes for these patients.

In particular, allogenic HCT provides a chance for long-term disease control in younger patients who have experienced multiple relapses.

2019 Transplantation and Cellular Therapy Meetings

Sergio A. Giralt, MD, discusses the role of allogeneic hematopoietic cell therapy in patients with multiple myeloma.

Sergio A. Giralt, MD

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