Early MRD Guides Therapy in Mantle Cell Lymphoma

Julie Chang, MD

Omitting maintenance therapy in patients with mantle cell lymphoma (MCL) achieving minimal residual disease (MRD)-negativity following treatment did not affect progression-free survival (PFS), according to Julie Chang, MD.¹

A study sought to see if MRD testing could be used to identify patients with MCL who may not need maintenance therapy and enrolled 21 patients who were not eligible for intensive treatments.

Once enrolled, patients received bendamustine and obinutuzumab (Gazyva) induction followed by consolidation obinutuzumab. Patients who had a complete response and negative MRD in both peripheral blood and bone marrow aspirate after consolidation obinutuzumab did not receive maintenance therapy.

ClonoSEQ assessed MRD status in peripheral blood and was used to establish a link between early response and outcomes within the study.

Researchers also found that bendamustine-based induction therapy with obinutuzumab remained a standard of care for older adult patients with MCL, and MRD testing was good at predicting patients who would benefit from maintenance therapy and those who would not.

In an interview with Targeted Oncology^TM, Chang, associate professor of medicine at the University of Wisconsin School of Medicine and Public Health, discussed the MRD-adapted study in patients with previously untreated MCL and the key findings from the trial.

Cancer cells and cancerous malignant cell tumour growth in a human body caused by carcinogens and genetics, leukemia or lymphoma, chemotherapy or radiation therapy: © Rick - stock.adobe.com

Targeted Oncology: What was the rationale behind this research?

Chang: We know that patients who are older and not eligible for intensive therapies can have limited options for frontline therapy that's tolerable. We were very interested in using the novel monoclonal antibody, obinutuzumab and combining it with bendamustine. We know that from the results of the GALLIUM study [NCT01332968] in other types of low-grade non-Hodgkin lymphomas that resulted in better progression-free survival compared with bendamustine and rituximab [Rituxan]. We were hoping to capitalize on that same benefit in [patients with] mantle cell lymphoma.

We are also interested in seeing if minimal residual disease testing could predict the need for maintenance therapy. Maintenance therapy has been very controversial, or there's been mixed data about the benefit of that modality, so we are very interested in seeing if there was some biological predictor for benefit.

What were the methods and design of the study?

This was a risk-adapted therapy that was individual to the patient. This was a phase 2, open-label study. All patients received bendamustine and obinutuzumab for 6 treatment cycles. Based on their response after 6 cycles of bendamustine and obinutuzumab followed by a consolidation course of 4 weekly doses of obinutuzumab, they underwent minimal residual disease testing in both the blood and the bone marrow. If they were negative by minimal residual disease testing in both of those areas, they would go on to observation. If they had features of minimal residual disease positivity, they would go on to receive 8 more cycles of maintenance obinutuzumab.

Please explain the main findings from this research.

There were a few interesting findings from our study. Firstly, the progression-free survival at 2 years was not different between patients who received maintenance therapy or not. We would interpret that data as saying that minimal residual disease testing is good at predicting patients who would benefit from maintenance therapy or not. We feel like that is a biologically rational way of guiding therapy.

The other interesting aspect of the study is that we did do minimal residual disease testing in the blood only after 2 cycles of induction therapy. We saw a significant difference in progression-free survival at 2 years among patients that were already negative in the peripheral blood on their MRD study vs those that were persistently positive. In fact, the progression-free survival at 2 years was nearly doubled and patients that were MRD-negative refer to cycles of therapy.

Within mantle cell lymphoma, there can be significant heterogeneity in terms of clinical behavior. This may help us understand patients even sooner in their treatment course, who may benefit from intensification of therapy.

Where does research move forward from here?

There are many avenues of interest in mantle cell lymphoma. With all of the new novel targeted therapies, bispecific [antibodies], we are looking at incorporating more targeted therapies or immunotherapies, into even frontline treatment of mantle cell lymphoma. The interesting part of this study is using minimal residual disease testing results to help us predict outcomes or identify individuals who may not be responding adequately to their initial course of treatment.

What are the key takeaways from this trial?

Bendamustine-based induction therapy does remain a standard for older adults with mantle cell lymphoma. We do see ongoing consistent good results at 2 years post treatment as supported by our study. I think it is important for community-based oncologists to be aware of the availability of minimal residual disease testing and understand that those might be helpful pieces of information when trying to identify patients who may need a different treatment modality.

REFERENCE:

McQuinn D, Hyun M, Kim K, et al. Minimal residual disease (MRD) testing by next generation sequencing (NGS) after two cycles (cy) of non-intensive chemoimmunotherapy is predictive of remission duration and need for maintenance therapy (MT) in previously untreated mantle cell lymphoma (MCL): a Wisconsin Oncology Network study. Blood. 2023;142(suppl 1):4407. doi:10.1182/blood-2023-180381