Reem Karmali, MD, MS

Reem Karmali, MD, MS, an assistant professor of medicine (hematology and oncology) at Northwestern University's Feinberg School of Medicine, discusses next steps for optimizing maintenance therapy in older patients with mantle cell lymphoma (MCL).

An analysis examining clinical outcomes and predictors of survival in older patients with MCL in the era of rituximab (Rituxan) was presented at the 

. With respect to the future, the big question is how to optimize maintenance approaches for older patients with the disease, says Karmali. In a trial at Northwestern University’s Feinberg School of Medicine,investigators are examining ibrutinib (Imbruvica) maintenance therapy for up to 4 years in patients of all age groups, including those who are older. Some insight may be gained regarding whether single-agentibrutinib as maintenance would be beneficial in this particular patient population, explains Karmali.

Other ongoing trials are examining therapeutic strategies specifically in older patients with MCL, adds Karmali, one of which is the phase 3 SHINE study. In this study, patients with MCL over the age of 65 are being treated with bendamustine/rituximab (Rituxan) as a backbone with or without ibrutinib. Investigators are also addressing whether ibrutinib with rituximab versus rituximab monotherapy as a maintenance strategy would be useful.

Another European trial, the phase 3 MCL R2 Elderly trial, is being conducted to see whether lenalidomide (Revlimid) is an appropriate strategy for the maintenance setting. Many ongoing trials will address optimization of maintenance approaches in elderly patients with the disease, concludes Karmali.

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Reem Karmali, MD, MS, discusses next steps for optimizing maintenance therapy in older patients with mantle cell lymphoma.

Dr. Karmali on Optimizing Maintenance Therapy in Older Patients With MCL

Reem Karmali, MD, MS, assistant professor of medicine, Northwestern University Feinberg School of Medicine, discusses the limitations of intensive therapy in older and medically unfit patients with mantle cell lymphoma (MCL).

MCL is a rare and aggressive subtype of B-cell non-Hodgkin lymphoma, says Karmali. The majority of patients who are diagnosed with MCL are older. Additionally, these patients may have comorbidities or be medically unfit, thereby limiting their ability to undergo intensive chemoimmunotherapy with or without an autologous stem cell transplant (ASCT).

As such, these patients may have poorer outcomes, says Karmali. To that end, researchers conducted an analysis that evaluated the practice patterns and survival outcomes of patients 65 years of age or older with newly diagnosed MCL. The results were presented during the 2020 ASCO Virtual Scientific Program.

Reem Karmali, MD, MS, discusses the limitations of intensive therapy in older and medically unfit patients with mantle cell lymphoma (MCL).

Dr. Karmali on Limitations of Intensive Therapy in Older/Medically Unfit Patients With MCL

Reem Karmali, MD, MS, assistant professor of medicine, Northwestern University Feinberg School of Medicine, discusses the next steps for research regarding the use of ibrutinib (Imbruvica) as maintenance therapy in mantle cell lymphoma (MCL).

A study that examined ibrutinib maintenance following intensive induction therapy showed that the approach is feasible and the toxicities are manageable, says Karmali. However, longer follow-up data are needed, as well as analysis of patients’ minimal residual disease (MRD) status. The primary objective of the study was to look at efficacy, which was assessed according to the rate of 3-year progression-free survival (PFS) rates.

However, an exploratory analysis looked at MRD status and an IgH polymerase chain reaction, based methodology. Investigators believe that MRD will provide better insight into whether patients can achieve deeper responses with ibrutinib maintenance. With this analysis, researchers hope to show a correlation between MRD status and PFS and overall survival that would warrant further exploration of ibrutinib maintenance, concludes Karmali.

Dr. Karmali on Next Steps of Research Regarding Ibrutinib Maintenance in MCL

Reem Karmali, MD, MS, assistant professor of medicine, Northwestern University Feinberg School of Medicine, discusses the toxicity profile of ibrutinib (Imbruvica) maintenance therapy after induction therapy in patients with mantle cell lymphoma (MCL).

Among the 36 patients who received ibrutinib as maintenance at a dose of 560 mg daily for up to 4 years or until disease progression or unacceptable toxicity, investigators reported toxicities that were in line with what one would expect from ibrutinib's safety profile. Overall, with treatment exposures, patients tolerated the drug quite well, says Karmali. At a follow-up of 19 months, the median number of cycles delivered were 16.5. One-quarter of patients have already completed 2 or more years of ibrutinib maintenance; of these patients, 2 of them have completed the full 4 years of treatment.

Regarding toxicities, approximately two-thirds of patients had treatment-related adverse events that required dose modification. About 20% of patients required a permanent dose modification or reduction and 25% of patients discontinued ibrutinib permanently. Atrial fibrillation was the main cause for discontinuation, and it was reported in 9 patients, concludes Karmali.

Reem Karmali, MD, MS

Articles

Dr. Karmali on Optimizing Maintenance Therapy in Older Patients With MCL

Dr. Karmali on Limitations of Intensive Therapy in Older/Medically Unfit Patients With MCL

Dr. Karmali on Next Steps of Research Regarding Ibrutinib Maintenance in MCL

Dr. Karmali on the Toxicity Profile of Ibrutinib Maintenance in MCL