Shift in MCL Induction Therapy Has Led to Improvement in Event-Free Survival in Real World

The shift in the pattern of care in mantle cell lymphoma (MCL) to bendamustine (Treanda) and rituximab (Rituxan; BR) in the frontline has resulted in an improvement in event-free survival (EFS) compared with the era in which R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) dominated front-line treatment.

The 3-year rate of EFS was 45.9% during the era in which R-CHOP or R-CHOP-like induction therapy was used predominantly compared with 58.4% in the era of BR, representing a hazard ratio (HR) of 0.69 (95% CI, 0.51-0.92;P= .006).

Rates of autologous stem cell transplant (ASCT) were similar in the 2 eras, although the use of high-dose cytarabine (HiDAC) in induction has increased.

These were the findings from a prospective population-based analysis of patients with newly diagnosed MCL by investigators led by Alessia Castellino, MD, from A.O. Città della Salute e della Scienzadi Torino, Italy, and the Hematology Department, Mayo Clinic, Rochester, Minnesota. They presented their data in a poster at the 2018 American Society of Hematology meeting.

MCL outcomes data come primarily from clinical trials, which don’t characterize the impact of therapeutic advances on pattern of care and outcomes in the general population, the investigators declared as a rationale for their study. “Our aims were to describe the real world situation of patients included in a prospective register,” said Castellino.

“In Italy where I’m working, as in the US (Mayo Clinic), where I conducted this study, we use rituximab and bendamustine as standard of care for patients with MCL older than 65 to 70 years, who cannot receive intensive care with R-CHOP or alternatively R-DHAP [rituximab plus dexamethasone, cytarabine, and cisplatin] plus ASCT,” she said.

A total of 348 adult patients with newly diagnosed MCL who were prospectively enrolled into the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE) Molecular Epidemiology Resource were enrolled. Patients were actively followed for retreatment, relapse, and death. Era 1, before the introduction of BR into practice, was defined as September 1, 2002 to December 31, 2009. Era 2 was defined as January 1, 2010 until June 30, 2015. Outcomes were compared between the 2 eras.

Five patients with missing or unknown information on front-line treatment were excluded, leaving 343 for the analysis: 169 who were diagnosed in era 1 with a median follow-up of 131.2 months and 174 in era 2 with a median follow-up of 58.9 months.

Baseline clinical characteristics and Mantle Cell Lymphoma International Prognostic Index (MIPI) score were similar across the 2 eras, with 22% classified as high risk and 31% as intermediate risk based on MIPI score.

Front-line induction treatment was significantly different between the 2 eras (P<.001). Whereas R-CHOP or R-CHOP-like induction therapy dominated in era 1, used in 53% of the patients, regimens were more evenly distributed in era 2 between BR-based treatment (28%), R-CHOP/R-CHOP-like treatment (26%), and HiDAC-based regimens (16%). HiDAC was used in only 1% of patients in the R-CHOP era.

Intensified regimens, such as hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethaspone), were used in 9% of participants in era 1 and 5% in era 2. Other regimens such as R-cladribine, R-fludarabine-mitoxantrone, and R monotherapy were used in 21% in era 1 and 7% in era 2. The rate of observation, radiation therapy, or surgery only was similar between eras 1 and 2 (15% vs 18%, respectively).

ASCT as consolidation of first-line treatment or use of rituximab maintenance was not different between the 2 eras. ASCT as consolidation was performed in 28% in each era. Rituximab maintenance was used in 9% in era 1 and 11% in era 2.

Median overall follow-up was 83.8 months (131.2 months in era 1 vs 58.9 months in era 2). Among the entire cohort of 343 patients with MCL, the 3-year EFS rate was 51.9%. The 3-year rate of EFS was 45.9% during era 1 and 58.4% in era 2, and the MIPI-adjusted HR for EFS by treatment era was 0.70 (P= .01).

A total of 155 patients died during follow-up, with no difference in the rate of death between the 2 eras (P= .390). The cause of death was lymphoma-related in about 62% in each era (P= .807). The 3-year rate of overall survival (OS) was 73.5% (95% CI, 68.8%-78.4%) in the entire cohort; 70.9% during era 1 versus 76.1% during era 2 (HR, 0.87; 95% CI, 0.61-1.24;P= .26). The MIPI-adjusted HR for OS by treatment era was 0.85 (P= .36).

&ldquo;While patterns of care in MCL continue to evolve, the introduction of bendamustine and high-dose cytarabine-based regimens resulted in an improvement in EFS but not OS in this observational cohort-based analysis,&rdquo; the investigators concluded.

Reference:

Castellino A, Larson MC, Maurer MJ, et al. Patterns of care and outcomes in mantle cell lymphoma in the modern immunochemotherapy era. Presented at: 2018 ASH Annual Meeting; Dec. 1-4, 2018; San Diego, CA. Abstract 4140.