The following article features coverage from the 2021 American Society of Hematology Annual Meeting. Click here to read more of Cancer Therapy Advisor’s conference coverage.

Long-term follow up of a phase 3 European Mantle Cell Lymphoma (MCL) Network trial confirmed the previous observation of significantly prolonged time to treatment failure (TTF) and longer overall survival (OS) with the addition of high-dose cytarabine to immunochemotherapy before autologous stem cell transplantation (ASCT) in patients with MCL aged 65 years or younger.1 These results were presented at the 2021 American Society of Hematology (ASH) Annual Meeting.

“The high-dose cytarabine-containing induction and ASCT achieves 60% survival at 10 years with acceptable toxicity,” said Olivier Hermine, MD, PhD, of the University of Paris in France, on behalf of the European MCL Network investigators.

In the randomized, open-label, phase 3 trial (ClinicalTrials.gov Identifier: NCT00209222), researchers sought to determine whether the introduction of high-dose cytarabine to immunochemotherapy before ASCT improved clinical outcomes.


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The study included 466 evaluable patients, aged 65 years or younger, with untreated stage II-IV MCL from 128 sites across 4 European countries.

The participants received either 6 cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by myeloablative radiochemotherapy and ASCT (control group, 234 patients) or 6 cycles of alternating R-CHOP or R-DHAP (rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) induction, followed by a high-dose cytarabine-containing conditioning regimen and ASCT (cytarabine group, 232 patients).

The median age of the patients was 55 years (range, 30-67), with similar MCL International Prognostic Index (MIPI) and Ki-67 in both arms.

In the initial analysis after a median follow-up of 6.1 years, patients who received high-dose cytarabine had a significantly longer TTF (median, 9.1 years; 5-year rate, 65%) compared with the control group (median, 3.9 years; 5-year rate, 40%; hazard ratio [HR], 0.56; P =.038).2

With extended follow-up of an additional 5 years, Dr Hermine and colleagues observed significant prolongation of the median OS, and the benefit of high-dose cytarabine was seen in both high- and low-risk patients.

The median TTF was 4.1 years in the R-CHOP arm and 7.7 years in the R-DHAP arm (P <.0001). The 10-year TTF was 27% in the R-CHOP arm and 43% in the R-DHAP arm (unadjusted HR, 0.60; 95% CI, 0.47-0.76; MIPI-adjusted HR, 0.56; 95% CI, 0.44-0.71; Ki67-adjusted HR, 0.52; 95% CI, 0.38-0.70; all P <.0001).

The median progression-free survival (PFS) from randomization was 4.3 years in the R-CHOP arm and 8.0 years in the R-DHAP arm (HR, 0.61; 95% CI, 0.48-0.78; P <.0001). The median PFS from the end of induction was 4.2 years in the R-CHOP arm and 8.5 years in the R-DHAP arm (HR, 0.60; 95% CI, 0.47-0.78; P <.0001). The median PFS from ASCT was 4.7 years in the R-CHOP arm and 10.8 years in the R-DHAP arm (HR, 0.53; 95% CI, 0.40-0.71; P <.0001).

At a median follow-up of 11.0 years, the median OS was not reached in the R-DHAP arm and was 11.3 years in the R-CHOP arm (P =.12). The 10-year OS was 55% in the R-CHOP arm and 60% in the R-DHAP arm (unadjusted HR, 0.80; 95% CI, 0.61-1.06; P =.12).

The OS was significantly superior in the R-DHAP arm after adjusting for MIPI score without Ki-67 (HR, 0.74; 95% CI, 0.56-0.98; P =.038) and with Ki67 (HR, 0.60; 95% CI, 0.41-0.87; P =.0066).

In patients with high-intermediate or high MIPI, the median OS was significantly better in the R-DHAP arm (10.4 years) than in the R-CHOP arm (5.0 years; HR, 0.55; 95% CI, 0.35-0.88; P =.013). In patients with low-intermediate or low MIPI, the median OS was not reached in the R-DHAP arm and was 14.4 years in the R-CHOP arm (HR, 0.37; 95% CI, 0.13-1.06, P =.064).

In high-risk patients, the median TTF was 2.8 years in the R-CHOP arm and 7.6 years in the R-DHAP arm (HR, 0.49; 95% CI, 0.32-0.74; P <.00078). In low-risk patients, the median TTF was not reached in the R-DHAP arm and was 5.3 years in the R-CHOP arm (HR, 0.56; 95% CI, 0.27-1.15; P =.11).

Although not statistically significant, the cumulative incidence of secondary hematologic malignancies was higher in the R-DHAP arm (9 events) than in the R-CHOP arm (4 events). The 10-year probability was 4.5% in the R-DHAP arm and 1.4% in the R-CHOP arm (P =.14).

Dr Hermine said it remains unclear whether it is best to avoid total body irradiation to reduce the rate of secondary malignancies after R-CHOP/R-DHAP. He said this chemotherapy regimen might cure some patients, and this therapy may challenge future chemotherapy-free strategies in MCL.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Read more of Cancer Therapy Advisor’s coverage of the ASH 2021 meeting by visiting the conference page.

References

  1. Hermine O, Jiang L, Walewski J, et al. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL younger): A long-term follow-up of the randomized, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Presented at ASH 2021; December 11-14, 2021. Abstract 380.
  2. Hermine O, Hoster E, Walewski J, et al. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. Published online August 6, 2016. doi:10.1016/S0140-6736(16)00739-X