Robert M. Dean, MD, assistant professor, Department of Medicine, School of Medicine, member, Hematopoietic and Immune Cancer Biology Program, Case Comprehensive Cancer Center, physician, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, discusses the potential role for consolidative CAR T-cell therapy in mantle cell lymphoma (MCL).

CAR T-cell therapy could be utilized as consolidative treatment for patients with MCL who achieve less than a complete response with frontline chemoimmunotherapy, says Dean. Historically, consolidative treatment has consisted of high-dose chemotherapy and autologous stem cell transplant after induction therapy for younger, fitter patients with MCL. 

Whether patients who achieve a deep molecular remission with undetectable minimal residual disease (MRD) require consolidative treatment remains an area of active clinical investigation, Dean explains. However, there may be rationale to suggest that CAR T-cell therapy could be a consolidative treatment for patients without the need for autologous transplant, Dean explains. Moreover, MRD testing could inform which patients could benefit from this approach rather than giving CAR T-cell therapy after clinical relapse or failure of BTK inhibitor therapy, concludes Dean. 

Videos

Robert M. Dean, MD, discusses the potential role for consolidative CAR T-cell therapy in mantle cell lymphoma.  



Dr. Dean on the Potential Role of Consolidative CAR T-Cell Therapy in MCL 

Robert M. Dean, MD, assistant professor, Department of Medicine, School of Medicine, member, Hematopoietic and Immune Cancer Biology Program, Case Comprehensive Cancer Center, physician, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, discusses remaining challenges in diffuse large B-cell lymphoma (DLBCL).

The recent approvals of polatuzumab vedotin-piiq (Polivy), selinexor (Xpovio), and the combination of tafasitamab-cxix (Monjuvi) and lenalidomide (Revlimid) have left the question of optimal sequencing unanswered for patients with DLBCL, Dean explains. Additionally, the generalizability of the results of the phase 2 trials that led to the approvals remains largely unknown, Dean says. 

Patients who have relapsed after an autologous stem cell transplant and CAR T-cell therapy and who are still eligible for additional therapy may be candidates for these newer regimens, Dean explains. However, treatment selection depends on the goals of the patient and the toxicity profiles of the agents.

Generating additional data to inform treatment selection beyond patient assessment may alleviate sequencing challenges in DLBCL, concludes Dean. 

Robert M. Dean, MD, discusses remaining challenges in diffuse large B-cell lymphoma.  



Dr. Dean on Remaining Challenges in DLBCL 

Robert Dean, MD, staff physician, Cleveland Clinic, discusses challenges in the mantle cell lymphoma (MCL) paradigm.

Many patients with MCL will progress over the course of treatment. Though chimeric antigen receptor (CAR) T-cell therapy has shown promising curative potential in other hematologic malignancies, its role in MCL is unclear. For select patients, allogenic bone marrow transplant or allogeneic stem cell transplant has proven beneficial. It is not advisable for the majority of patients, says Dean, due to the inherent risks of the procedure.

In the case of a younger, fit patient who has an appropriate donor and has previously received treatment with a BTK inhibitor, a CAR T-cell therapy clinical trial is recommended. Preliminarily, it seems to be an active therapeutic strategy, explains Dean. Though the short-term toxicities are not trivial, the longer-term toxicity profile is more favorable than what is seen historically with allogeneic transplant, adds Dean. Excluding that as an option, allogeneic transplant is a suitable option that can be discussed with a young and otherwise healthy patient.

Dr. Dean on Challenges in the MCL Paradigm

Robert Dean, MD, staff physician, Cleveland Clinic, discusses drugs that have been approved by the FDA for the treatment of patients with relapsed mantle cell lymphoma (MCL).

Bortezomib (Velcade) and lenalidomide (Revlimid) received approval in the United States, and temsirolimus (Torisel) was approved in Europe, says Dean. More recently, the BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence) were also granted approvals in the United States.

Both ibrutinib and acalabrutinib seem to show more activity in patients with MCL compared with earlier drugs that were approved in the relapsed setting, says Dean. There is a slightly higher rate of significant adverse events with ibrutinib, particularly issues associated with atrial fibrillation and bleeding. Most of these toxicities are minor but can be clinically serious. Dean adds that those 2 types of toxicities are relatively rare with acalabrutinib.

Robert Dean, MD, staff physician, Cleveland Clinic, discusses FDA approved drugs for patients with relapsed mantle cell lymphoma.

Dr. Dean on FDA Approved Drugs for Patients With Relapsed MCL

Robert Dean, MD, a staff physician at Cleveland Clinic, discusses ongoing research on biomarkers in mantle cell lymphoma (MCL).

There is a lot of interest in investigating biomarkers in MCL, explains Dean, as there is a high degree of genomic instability. Cyclin D1 translocation is one of the hallmarks of the disease, says Dean, and is known to be a common point of origin for lymphoma cells.

However, additional acquired mutations are also part of the biology of the disease, Dean explains. Physicians do not yet have great insight on how to use individual specific secondary mutations to predict outcome or select treatments, with the exception of 

 mutations, which are almost universally a poor prognostic indicator. Patients who harbor a 

 mutation may stand to benefit from a more aggressive third-line treatment if they received and progressed on a BTK inhibitor after frontline treatment, Dean concludes.

Dr. Dean Discusses Ongoing Research on Biomarkers in MCL

Robert Dean, MD, staff physician, Cleveland Clinic, discusses the evolution of treatment approaches in mantle cell lymphoma (MCL).

The treatment of MCL has evolved in a step-wise manner over the past 20 years, says Dean. Studies have shown the value of incorporating the monoclonal antibody, rituximab (Rituxan) into frontline therapy.

Frontline therapy now consists of 2 approaches depending on the patient’s performance status, explains Dean. Younger, fitter patients typically receive a more intensive regimen that consists of combination chemotherapy followed by consolidation with high-dose chemotherapy, an autologous transplant, and then rituximab maintenance. Patients who are older with a lower performance status will generally receive a less intensive upfront chemotherapy, such as bendamustine and rituximab, rituximab maintenance without consolidation, and an autologous transplant.

For both populations, incremental advances in frontline treatment approaches have improved outcomes, but patients still face a high rate of mortality at the time of relapse, says Dean. Although initial remissions and survival have improved, physicians have to work harder to bring more options to patients who relapse, concludes Dean.

Robert Dean, MD

Articles

Dr. Dean on the Potential Role of Consolidative CAR T-Cell Therapy in MCL

Dr. Dean on Remaining Challenges in DLBCL

Dr. Dean on Challenges in the MCL Paradigm

Dr. Dean on FDA Approved Drugs for Patients With Relapsed MCL

Dr. Dean Discusses Ongoing Research on Biomarkers in MCL

Dr. Dean on the Evolution of Treatment Approaches in MCL