EHA 2016: News in Hematology - Overall Survival Outcomes in Patients with Mantle Cell Lymphoma (MCL) treated with Ibrutinib

EHA 2016. Abstract S438. Overall Survival Outcomes in Patients with Mantle Cell Lymphoma (MCL) treated with Ibrutinib in a Pooled Analysis of 370 Patients from 3 International Open-Label Studies

Simon Rule et al. 

Results: Overall, 370 patients were included in this analysis (PCYC-1104, n=111; SPARK, n=120; RAY, n=139); median age was 67.5 years, 94% had ECOG 0-1, 45% and 32% had intermediate and high-risk sMIPI, most patients had 1-3 prior lines of therapy (27%, 29%, 22% had 1, 2, 3 prior lines of therapy, respectively), 49% had bulky disease (>5 cm) and 88% had non-blastoid histology. Overall response rate (ORR) was 66% (20% CR; 46% PR), with a median DOR, PFS and OS of 18.6, 12.8 and 25.0 months, respectively. ORR (CR) for patients with 1, 2 and ≥3 prior lines of therapy was 77.8% (34%), 71% (24%) and 64% (16%). Of patients who achieved a CR, 70% were progression-free and 90% were alive at 2 years. Univariate analyses showed that patients with 1 vs >1 prior line of therapy had significantly longer OS, with longer OS also observed in those who were younger and had non-blastoid histology (Fig.), non-bulky disease or better sMIPI score. Patients with blastoid and non-blastoid histology had similar ORR (55 vs 72%) and time to best response (2.2 vs 2.1 months); however, DOR (8.6 vs 18.8 months), PFS (5.1 vs 14.6 months) and OS (12.8 vs not reached) were significantly shorter in patients with blastoid histology. Multivariate analyses identified ECOG, sMIPI, bulky disease and blastoid histology as impacting OS, and sMIPI, bulky disease, blastoid histology and 1 prior line of therapy as impacting PFS.

Conclusion: Here we show that OS is significantly longer in ibrutinib-treated patients who are younger and who have fewer prior lines of therapy, better sMIPI scores, non-bulky disease and non-blastoid histology. While PFS and OS in patients with blastoid vs non-blastoid histology are shorter, these rates are higher than seen with other agents, indicating that ibrutinib is an effective agent to achieve a response and potentially provide a bridge to transplant. Multivariate analyses indicate that traditional poor prognostic factors adversely impact OS, suggesting that worsening OS in later lines of therapy is associated with disease characteristics rather than an impact of ibrutinib on postprogression survival. Data support the preferential use of ibrutinib after initial vs later relapse, as PFS and OS are longer in patients receiving 1 vs >1 prior line of therapy.

CARE Faculty Perspective: Ibrutinib clearly appears to be the preferred strategy for patients with relapsed/refractory mantle cell lymphoma. This study highlights the inferior outcomes of multiply treatment MCL and supports the use of active agents such as ibrutinib earlier in the disease course.