Rory McCulloch, MD, vice chair, South West Peninsula, HaemSTAR, hematology registrar, University Hospitals, Plymouth, discusses the likelihood of relapse on a BTK inhibitor in mantle cell lymphoma (MCL).

BTK inhibitors have revolutionized the treatment landscape of MCL, but the data show that approximately half of patients will not have a durable response. Ultimately, every patient will end up relapsing at some point, says McCulloch. The field is reaching the stage where the majority of patients have been exposed to a BTK inhibitor and are at the point of relapse. The question now is what to do next.

Early data have shown that it is a very difficult point in the treatment algorithm and there have been no satisfactory treatments that have surfaced, says McCulloch. The average response rate is typically about 30%. Moreover, the progression-free survival, in the best study, which was with venetoclax (Venclexta), is only about 3 months. This reflects a large unmet need, which investigators are hoping to fill with novel regimens.

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Dr. McCulloch on the Likelihood of Relapse on a BTK Inhibitor in MCL

Rory McCulloch, MD, vice chair, South West Peninsula, HaemSTAR, hematology registrar, University Hospitals, Plymouth, discusses the use of R-BAC (rituximab [Rituxan],bendamustine, and cytarabine) in patients with mantle cell lymphoma (MCL) who had progressed on initial therapy with a BTK inhibitor.

In a retrospective study, McCulloch and investigators examined the use of R-BAC in patients who had progressed on initial therapy with a BTK inhibitor. Although R-BAC is recommended for use in patients with MCL, it is not a suitable regimen for everyone, as it does carry a high rate of hematologic toxicity. This can, however, be offset to a certain extent by attenuating the doses.

The oldest patient enrolled in the trial was 79-years-old. The patient had a short response to ibrutinib (Imbruvica) and was subsequently given 1 dose of bendamustine and cytarabine. He tolerated the regimen fairly well and went on to have a response that lasted over 2 years, says McCulloch. This serves as proof that the regimen should not be restricted on the basis of age. Rather, the prognosis of the patient and their fitness should be weighed against the potential toxicities and dosing schedules of the regimen.

Dr. McCulloch on the Use of R-BAC in MCL After Progression on BTK Therapy

Rory McCulloch, MD, vice chair, South West Peninsula, HaemSTAR, hematology registrar, University Hospitals, Plymouth, discusses data supporting the use of R-BAC (rituximab [Rituxan], cytarabine, and bendamustine) in mantle cell lymphoma (MCL).

Initial research in Italy led to the establishment of R-BAC as a standard therapy for patients with MCL. Both bendamustine and cytarabine are known to work very well in this disease, so it’s logical that the regimen would induce a synergistic effect and high response rates in patients, says McCulloch.

Although there are many treatment regimens to choose from for patients with MCL, R-BAC has been shown to induce particularly impressive response rates. In a retrospective study led by McCulloch, the response rate was approximately 85% in patients who had progressed on initial therapy with a BTK inhibitor. Several of these responses were quite durable, lasting over 1 year. This regimen is a great option, particularly for younger patients who are fit enough to receive an allograft transplant. However, age should not deter physicians from administering this regimen, he adds. With appropriate dose modifications, older patients can receive this regimen as well.

Rory McCulloch, MD

Articles

Dr. McCulloch on the Likelihood of Relapse on a BTK Inhibitor in MCL

Dr. McCulloch on the Use of R-BAC in MCL After Progression on BTK Therapy

Dr. McCulloch on Data Supporting the Use of R-BAC in MCL