ASH 2022: MCL Trials Break New Ground, May Change Practice

Mantle cell lymphoma (MCL) research presented at the 2022 ASH Annual Meeting broke new ground, showed promising early results, and could change practice, according to researchers.

Results of the phase 3 TRIANGLE trial may change practice, as they suggest that younger, fit MCL patients may be able to forgo autologous stem cell transplantation (ASCT).1 The trial showed that MCL patients who received ibrutinib-containing induction and maintenance without ASCT had similar failure-free survival (FFS) to patients who received chemoimmunotherapy induction and ASCT without ibrutinib.

The phase 2 TARMAC trial broke new ground, showing that ibrutinib and tisagenlecleucel can produce a high rate of complete response (CR) in patients with relapsed or refractory MCL.2 This was the first study on the combination of ‘ n BTK inhibitor and anti -CD19 chimeric antigen receptor (CAR) T cell therapy in patients with MCL.

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Promising early results were seen in a phase 1/2 trial of glofitamab.3 The bispecific antibody produced durable CRs in patients with heavily pretreated MCL.

Researchers also observed promising early results in a phase 1b trial of zandelisib and zanubrutinib.4 The combination produced a high response rate in patients with relapsed or refractory MCL.

Ibrutinib may eliminate the need for ASCT

Results of the TRIANGLE trial showed that the addition of ibrutinib to chemoimmunotherapy induction and the use of ibrutinib as maintenance after ASCT can improve FFS in patients with transplant-eligible MCL.1 In addition, patients receiving ibrutinib-containing induction and maintenance received without ASCT had similar FFS to patients who received chemoimmunotherapy induction and ASCT without ibrutinib.

The phase 3 trial (ClinicalTrials.gov Identifier: NCT02858258) included 870 patients with previously untreated, stage II-IV MCL who were eligible for transplantation. Patients were randomly assigned to 3 treatment arms.

In the control arm, patients received induction with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) or R-DHAP (rituximab, dexamethasone, cytarabine and cisplatin) followed by ASCT and observation (n=288).

In the second arm, patients received R-CHOP/R-DHAP induction plus ibrutinib, followed by ASCT and 2 years of ibrutinib maintenance (n=292). The third arm received R-CHOP/R-DHAP induction plus ibrutinib and 2 years of ibrutinib maintenance (n=290).

FFS was significantly better for patients who received induction with ibrutinib followed by ASCT and ibrutinib maintenance than for patients in the control arm. The 3-year FFS rate was 88% in the ibrutinib-ASCT arm and 72% in the control arm (hazard ratio [HR], 0.52; P =.0008).

FFS was not significantly different for patients in the control arm and for those who received ibrutinib induction and maintenance without ASCT. The 3-year FFS rate was 86% in the ibrutinib-alone arm and 72% in the control arm (HR, 1.77; P =.9979).

More than half of patients in each of the 3 treatment arms also received rituximab maintenance, but there was no difference in efficacy by receipt of rituximab maintenance.

A comparison of the 2 ibrutinib-containing arms (with and without ASCT) is still ongoing.

“There is currently no decision on whether ASCT does add to ibrutinib, but so far toxicity only favors ibrutinib,” says study presenter Martin Dreyling, MD, of LMU University Hospital Munich in Germany.

During induction, rates of grade 3–5 adverse events (AEs) were similar with and without ibrutinib. During follow-up, there were more grade 3-5 AEs in the ASCT-ibrutinib arm than in the control arm and the ibrutinib-alone arm.

“The important and interesting finding of this study is that patient outcomes for those who received NORDIC-style chemotherapy with ibrutinib without a transplant were actually equivalent to those who did receive a transplant,” says Brian T. Hill, MD, PhD, from Cleveland Clinic in Ohio, who was not involved in this study.

Brian T. Hill, MD, PhD

“This suggests that, in younger transplant-eligible MCL patients, if they receive the NORDIC induction regimen with a BTK inhibitor, they can be effectively treated without a transplant and the morbidity and potential for late effects of this avoid maneuver. However, the main caveat of the study is that only about half of the patients in the control arm received maintenance rituximab, which is a maneuver that has been shown to improve progression-free survival and overall survival after ASCT for MCL.

The results of TRIANGLE are “potentially practice-changing,” said Christopher R. Flowers, MD, of the University of Texas MD Anderson Cancer Center in Houston, who was not involved in conducting this study but gave an introductory presentation on it. delivered at ASH 2022.

“These provocative results raise the potential to avoid first-line autologous transplantation in younger, fit patients,” said Dr. Flowers.