Early Relapse Following Intensive and Non-Intensive Frontline Therapy Indicative of Inferior Survival in Mantle Cell Lymphoma

Progression of disease (POD) within 24 months appeared to be associated with inferior survival among patients with mantle cell lymphoma (MCL) who have received either intensive or less intensive frontline therapy, with those who progressed within 6 months experiencing the highest risk of early mortality, according to findings published in Blood Advances.

The median overall survival (OS) from first progression among relapsed individuals was 1.3 years (95% CI, 0.9-2.4) for patients who had POD within 6 months, 3 years (95% CI, 2.0-6.8) for those who had POD within 6 to 24 months, and 8 years (95% CI, 6.3–not reached [NR]) for patients who had POD after 24 months. Additionally, the second median progression-free survival (PFS2) was 1 year (95% CI, 0.4-1.3), 1 year (95% CI, 0.8-1.4), and 2.3 years (95% CI, 1.8-3.2) for patients in the 6 month, 6 to 24 months, and over 24 months cohorts, respectively.

“To our knowledge, this represents the largest report to date describing the prognostic significance of time to first relapse in patients with MCL. Consistent with prior literature, POD within 24 months of intensive therapy was associated with increased risk for early mortality both in the training and validation cohorts, identifying a high-risk population which may be preferentially selected for investigation of novel therapies in the second line setting. Additionally, we observed a strong association between time to POD and OS2 among patients treated with less-intensive frontline treatment. This association was replicated in the validation cohort including in the subgroup of patients treated with BR, which is currently a widely used frontline regimen,” the authors wrote.

The study’s training cohort included those who were 18 years of age or older who had been diagnosed with MCL and treated between 2000 to 2017. Patients who had documented relapse following frontline treatment were categorized into 3 groups, including those with refractory disease defined as progressive or POD within 6 months of diagnosis, POD between 6 to 24 months of diagnosis, and POD after 24 months from diagnosis.

The validation cohort included adult patients with MCL who had received a frontline treatment of bendamustine and rituximab (Rituxan), cyclophosphamide, vincristine, and prednisone (R-CHOP) or rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP).

Investigators identified 1168 patients with MCL. The population had a median PFS of 4.6 years, as well as a median follow up of 3.5 years following diagnosis. In total, 455 patients had documented relapsed following frontline treatment and were included in the analysis. This population had a median follow up of 2.6 years from first progression. Approximately half of this population (54%) received a frontline treatment that was considered intensive. Common frontline therapies included rituximab, hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone plus alternated high dose cytarabine and methotrexate (26%); R-CHOP (25%); bendamustine rituximab (19%); and rituximab with methotrexate, cyclophosphamide, vincristine, doxorubicin, and prednisone plus high dose cytarabine (10%).

In total, 14% of patients had POD within 6 months, 36% had POD within 6 to 24 months, and 52% had POD after 24 months.

Additional findings from the study indicated that patients who had POD after 6 months who received a less intensive frontline therapy had a median OS2 of 2 years (95% CI, 0.9-4.5) following relapse, as well as 6.8 years (95% CI, 3.1-9.7) and 10.5 years (95% CI, 5.8-NR) among those whose POD occurred at 6 to 24 months and more than 24 months, respectively. Additionally, the median OS2 among those who received intensive therapy was 0.9 years (95% CI, 0.4-3.0), 2 years (95% CI, 1.1-3.4), and 9.5 years (95% CI, 4.8-NR) in each of the respective cohorts.

“Further study is warranted to better characterize the biology of this high-risk patient population. These findings have implications for clinical practice and to inform the selection of high-risk patients for future prospective therapeutic studies in relapsed MCL,” the investigators concluded.

Reference

Bond Da, Switchenko JM, Villa D, et al. Early relapse identifies MCL patients with inferior survival after intensive or less intensive frontline therapy. Blood Adv. Published online September 13, 2021. doi:10.1182/bloodadvances.2021004765