Predictive factors and outcomes for ibrutinib in relapsed/refractory marginal zone lymphoma: a multicenter cohort study.

Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: "ibrutinib responders"-patients who achieved complete or partial response (CR/PR) to ibrutinib; "stable disease (SD)"; and "primary progressors (PP)"-patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% ORR/CR, 29% with SD, and 13% with PP. The median PFS and OS were 29 and 71.4 months, respectively, with no difference in PFS or OS based on the ibrutinib line of therapy or type of therapy before ibrutinib. Patients with complex cytogenetics had an inferior PFS (HR = 3.08, 95% CI 1.23-7.67, p = 0.02), while those with both complex cytogenetics (HR = 3.00, 95% CI 1.03-8.68, p = 0.04) and PP (HR = 13.94, 95% CI 5.17-37.62, p < 0.001) had inferior OS. Only primary refractory disease to first-line therapy predicted a higher probability of PP to ibrutinib (RR = 3.77, 95% CI 1.15-12.33, p = 0.03). In this largest study to date evaluating outcomes of R/R MZL treated with ibrutinib, we show that patients with primary refractory disease and those with PP on ibrutinib are very high-risk subsets and need to be prioritized for experimental therapies.

The Multidisciplinary Management of Colorectal Cancer: Present and Future Paradigms.

As treatment strategies for patients with colorectal cancer advance, there has now become an ever-increasing need for multidisciplinary teams to care for these patients. Recent investigations into the timing and duration of perioperative therapy, as well as, the rise of molecular profiling have led to more systemic chemotherapeutic options. The most efficacious use, in terms of timing and patient selection, of these therapies in the setting of modern operative and radiotherapy techniques requires the generation of care teams discussing cases at multidisciplinary conferences. This review highlights the role of multidisciplinary team conferences, advances in perioperative chemotherapy, current clinical biomarkers, and emerging therapeutic agents for molecular subtypes of metastatic colon cancer. As our understanding of relevant molecular subtypes increases and as data becomes available on treatment response, the treatment of colorectal cancer will become more precise and effective.