Peter Martin, MD

Peter Martin, MD, associate professor of Medicine and chief of the Lymphoma Program at Weill Cornell Medicine, explains the importance of reviewing real-world databases and the results of a real-world study of treatment patterns and outcomes of patients with mantle cell lymphoma (MCL).

Data from community-based practices in the United States obtained though the Flatiron Health Electronic Health Records were retrospectively reviewed to determine how treatment of MCL in the real-world and outcomes of these patients align with what has been observed in clinical trials, according to Martin.

The study showed that treatment patterns differ from what has been deemed standard of care in prospective clinical trials. The results also showed that outcomes are worse across the board.

MCL is a fairly heterogeneous type of lymphoma, where some people present with a lymphoma that can be observed for several years. Other people's form of MCL is considerably more aggressive, and they can progress very quickly.

In clinical trials that maybe tend to enroll a slightly more homogeneous population, we see outcomes that have consistently improved over the years, so that in younger patients treated with intensive induction consolidation maintenance regimens, we have remission durations that will often last 7 to 9 years.

Data recently presented by Mitchell R. Smith, MD, PhD from the phase 2 ECOG-ACRIN E1411 trial demonstrated that in primarily older patients treated with abendamustine/rituximab backbone, followed by rituximab-based maintenance with a median progression-free survival about 5 years, those are probably the most standard approaches currently used today for MCL.

 We reported on data from the Flatiron dataset. Eighty percent of patients came from community-based practices, which was a total of about 4,000 patients. We looked at the data with 3 goals in mind. One was to evaluate patterns of care to know what treatments are actually being applied. We also wanted to look at patient outcomes to see how well the patients fare when treated in general practice mostly outside of clinical trials. Third, we were curious about the role of autologous stem cell transplantation in younger patients. Separately, we also looked at rituximab maintenance.

 We found that practice patterns did not entirely parallel what you might expect from clinical trials. So, we discussed what we would expect from clinical trials and what we found was that of older patients, probably only about 40%, are currently treated with bendamustine/rituximab. In younger patients, it was only about a quarter of all patients who are treated with cytarabine-based induction, but those numbers are a little bit lower than what you might expect based on guidelines and clinical trials.

Similarly, we found that the outcomes of patients were also not consistent with what you would expect from clinical trials. An average time to next treatment in a 2-year timeframe in both older and younger patients was a little bit longer in younger patients and a little bit less than older patients. It was nowhere near the 5- to 7-year remission durations that we have come to expect from clinical trials.

Lastly, we also found that the role of stem cell transplantation is quite reasonably being questioned in clinical trials.

Videos

Peter Martin, MD, explains the importance of reviewing real-world databases and the results of a real-world study of treatment patterns and outcomes of patients with mantle cell lymphoma.

Real-World Treatment Patterns and Outcomes Differ from Clinical Trials in MCL

Peter Martin, MD, assistant professor of medicine, Division of Hematology/Oncology, Weil Cornell Medicine, discusses the differences between subgroups of mantle cell lymphoma (MCL). MCL is a heterogenous disease, and in the World Health Organization classification of lymphoid neoplasms, MCL has a leukemia non-nodal presentation, says Martin.

MCL cells that evolve from a cell that passes through the germinal center tend to be

-mutant, and behave more indolently, Martin says. These patients may also go on to develop a

mutation and blastoid transformation. The MCL cells that have not passed through the germinal center, on the other hand, represent more classic MCL subtypes. These patients tend to be

unmutated, and these patients have a worse prognosis, Martin says, compared with the non-nodal patients. However, about 20% of these patients can be observed for a significant period of time.

Other groups of patients with MCL that tend to do worse include the blastoid morphology that comes with a more proliferative state and those with

mutations or high p53 protein expression. Martin says that oftentimes, Ki-67, blastoid morphology, and p53 go hand-in-hand, but this is not universally true. These patients should be treated differently; patients with p53 mutations who are not blastoid, for example, can be managed with chemotherapy-free approaches. Patients with blastoid morphology and p53 mutations, however, should be offered allogenic stem cell transplant early on or be considered for a clinical trial with CAR T cells, Martin concludes.

Peter Martin, MD, discusses the differences between subgroups of mantle cell lymphoma. MCL is a heterogenous disease, and in the World Health Organization classification of lymphoid neoplasms, MCL has a leukemia non-nodal presentation, says Martin.

Exploring Approaches to Treating Different Subgroups of Mantle Cell Lymphoma

Peter Martin, MD, assistant professor of medicine in the Division of Hematology/Oncology at Weill Cornell Medical College, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses a phase I, open-label, multicenter trial of oral azacitidine (CC-486) plus R-CHOP in patients with high-risk, previously untreated diffuse large B-cell lymphoma, grade 3B follicular lymphoma, or transformed lymphoma.

Overall, 33 patients with DLBCL were enrolled in the dose-escalation phase of the trial. They were treated with 100 mg, 150 mg, 200 mg, or 300 mg of oral azacitidine, with the majority of the patients treated with 200 mg and 300 mg. The patients received 7 days of oral azacitidine prior to the first cycle of R-CHOP and 14 days of oral azacitidine prior to cycles 2 through 6. All patients received granulocyte-colony stimulating factor (G-CSF) on day 2 of each cycle of R-CHOP.

Peter Martin, MD,&nbsp;assistant professor of medicine in the Division of Hematology/Oncology at Weill Cornell Medical College, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses a phase I, open-label, multicenter trial of oral azacitidine (CC-486) plus R-CHOP in patients with high-risk, previously untreated diffuse large B-cell lymphoma, grade 3B follicular lymphoma, or transformed lymphoma.

Azacitidine Plus R-CHOP in High-Risk DLBCL

Peter Martin, MD, assistant professor of Medicine, Division of Hematology/Oncology, Weill Cornell Medical College, discusses the evolving paradigm of treatment for mantle cell lymphoma. Martin says the evolution of the paradigm currently includes Bruton's tyrosine kinase inhibitor, phosphoinositide 3-kinase inhibitor, immunomodulatory treatments, and immunotherapies.

Peter Martin, MD, discusses the evolving paradigm of treatment for mantle cell lymphoma. Martin says the evolution of the paradigm currently includes Bruton's tyrosine kinase inhibitor, phosphoinositide 3-kinase inhibitor, immunomodulatory treatments, and immunotherapies.

Peter Martin, MD | Authors

Articles

Real-World Treatment Patterns and Outcomes Differ from Clinical Trials in MCL

Exploring Approaches to Treating Different Subgroups of Mantle Cell Lymphoma

Azacitidine Plus R-CHOP in High-Risk DLBCL

Dr. Peter Martin on Alternatives to Aggressive Therapy in Mantle Cell Lymphoma