Ongoing Research Aims to Better Define Role of ASCT in Myeloma

Marc J. Braunstein, MD, PhD

Although the emergence of novel therapies and quadruplet combinations have altered the frontline treatment paradigm in multiple myeloma, autologous stem cell transplantation (ASCT) still has a role in the treatment of this patient population, according to Marc J. Braunstein, MD, PhD, who added that ongoing research will continue to better identify patients most likely to derive benefit with its use.

“ASCT still plays a role for [patients with] multiple myeloma, particularly as a first-line treatment or after second-line treatment,” Braunstein stated during a presentation at the 41st Annual CFS^®.

In an interview with OncLive^®, Braunstein discussed the current role of ASCT for patients with multiple myeloma, highlighted the key factors used to determine patient eligibility, and detailed ongoing research centered around ASCT.

Braunstein is an associate professor in the Department of Medicine and the course co-director of the Hematology-Oncology System at New York University (NYU) Long Island School of Medicine; and the fellowship program director of Hematology/Oncology at NYU Langone Health.

OncLive: What is the value of examining the current role of ASCT in multiple myeloma?

Braunstein: I reviewed some of the randomized studies that have looked at whether conventional therapy or conventional therapy followed by stem cell transplant is superior. There is a lot of debate in the community, as well as in academia, [regarding] the role of ASCT [in] multiple myeloma now that we have novel therapies that have prolonged survival in absence of stem cell transplant.

I also reviewed some of the data for maintenance therapy after transplant and how that can potentially prolong survival. [Additionally], I touched on the role of minimal residual disease [MRD] testing and how that relates to the duration of maintenance after stem cell transplant.

What characteristics make patients eligible for stem cell transplant?

Eligibility for stem cell transplantation can sometimes be confusing, especially to people who are not involved in the process, which [includes] the majority of oncologists. Historically, age [served] as a hard cut off. A lot of the studies that have looked at stem cell transplantation for multiple myeloma have used 65 years of age as a cutoff. However, we now know that age is not the sole determining factor.

We can transplant patients well into their 70s. [Eligibility] depends on a variety of factors [other than] age, including performance status, other medical conditions, and frailty. We calculate a comorbidity index specific for [patients being considered for] stem cell transplant. All those data combined can help determine whether someone is truly fit or eligible for stem cell transplantation.

Is there any additional research needed to better determine if and when ASCT should be recommended for patients with multiple myeloma?

ASCT does still play a role for the treatment of multiple myeloma, particularly in high-risk patients. A lot of our [current] patients are receiving quadruplet regimens, and there are not [sufficient] randomized data in that setting to say whether someone who receives a quadruplet induction regimen still needs to go on to stem cell transplant.

Most of the randomized studies have looked at triplet induction regimens. There is still a need for those studies to look at whether quadruplet induction obviates the need for stem cell transplant.

Additionally, [determining] the optimal proteasome inhibitor to include with initial induction treatment [remains a debate], and there are several studies that have looked at including carfilzomib [Kyprolis] as part of the triplet or quadruplet induction regimen, and those have clearly showed a benefit, as have the studies looking at lenalidomide [Revlimid], bortezomib [Velcade], and dexamethasone, with or without a monoclonal antibody.

In the relapsed/refractory setting, adding carfilzomib clearly improves survival, including in high-risk patients, but we don't necessarily have head-to-head data with prior triplet induction regimens that have included either bortezomib or carfilzomib as the proteasome inhibitor of choice. In studies that have looked at triplet regimens in patients who did not go for stem cell transplant, there a difference has not been shown between a triplet containing bortezomib or carfilzomib in the up-front setting.

What are some complications associated with stem cell transplant in patients with multiple myeloma that clinicians should be aware of?

In general, ASCT is very safe for [patients with] multiple myeloma, and the rates of non-relapse mortality are very low, at less than 2%. This is due to very good stratification of patients to determine who’s most fit for stem cell transplantation and excluding those who would not do as well and have more comorbidities that make them ineligible for transplant.

The most common complications are infections. That's especially true during the initial period when the patient is very immunosuppressed before their engraftment. The most common cause of mortality after an ASCT is disease relapse—not anything specific to the transplant itself.

Is there anything you would like to add regarding ongoing investigations with stem cell transplant in multiple myeloma?

ASCT may not be for everybody, especially now that we understand that an MRD-negative status [is associated with] longer survival. Patients [who are MRD negative] may not need to go immediately to transplant after induction, especially if they're not high-risk.

We still need more data to determine the role of MRD [in] who should [select] to go for transplant, or [determining] how long to continue maintenance. However, there are several ongoing studies looking at that. The other thing is the optimal maintenance regimen after stem cell transplant. The convention is to use a single agent, such as lenalidomide, but we have many ongoing studies that are looking at combination therapy as maintenance.

How should ASCT be approached in 2023 for patients with multiple myleoma?

The most important thing, especially for an oncologist practicing in the community who is not necessarily focusing [solely] on the care of patients with multiple myeloma, is to refer patients to an expert who focuses on the care of patients undergoing stem cell transplantation. They can help determine if they are fit enough for transplant. You should then make a shared decision, because stem cell transplantation may not be suitable for everybody. You can make that decision, along with the transplant team, to determine if stem cell transplant is the optimal treatment for your specific patient.

Reference

Braunstein MJ. The role of stem cell transplant for MM in 2023. Presented at: 41st Annual CFS; November 8-10, 2023; New York, NY.