Tag: research publications

Brentuximab Vedotin is Efficacious as First Line Salvage Therapy in Patients with Relapsed/Refractory Hodgkin Lymphoma Prior to Autologous Hematopoietic Cell Transplantation

Picture1By Peter Martin, MD

Brentuximab vedotin (BV), is an antibody drug conjugate that selectively binds to a protein called CD30 on the surface of cells (e.g., Hodgkin lymphoma cells) and delivers a payload of toxin (monomethyl auristatin E) directly to that cell; i.e., a Trojan horse approach to cancer therapy. In 2011, the United States Food and Drug Administration (FDA) approved BV based on a phase II trial in which BV demonstrated an overall response rate (ORR) of 75% and complete response rate (CR) of 34% in patients with Hodgkin lymphoma that had relapsed following autologous hematopoietic cell transplantation (AHCT). Given the promising data, investigators at City of Hope and Weill Cornell Medical College-New York collaborated to evaluate the use of BV prior to AHCT. The standard approach for patients that relapse after first-line therapy includes cytotoxic chemotherapy followed by AHCT. However, this approach can be challenging for some patients and may be associated with some short-term and long-term toxicity. Use of BV prior to AHCT may cause patients some side effects and improve their quality of life prior to AHCT. Preliminary data from this trial were presented yesterday at the 56th Annual Meeting of the American Society of Hematology (ASH).

All patients had biopsy proven Hodgkin lymphoma that had relapsed following therapy with ABVD, BEACOPP, or a combination +/- radiation. Patients were treated with a standard dose of BV intravenously every 3 weeks for a maximum of 4 cycles. Over two-thirds of patients responded, including one third of patients that obtained a CR) and roughly half of the patients were able to proceed to AHCT without receiving additional chemotherapy. Treatments were well tolerated by all patients and no transfusions were required or neutropenic fevers developed.

The results from this trial suggest that BV may be an efficacious option as a first line salvage therapy. It is well tolerated and does not hinder stem cell collection or engraftment. Additional studies will be required to confirm these results. Moreover, this study may lay the groundwork for future studies with promising combinations.

Ibrutinib is a Highly Effective Therapy for Patients with Relapsed or Refractory CLL or SLL with 17p deletion: Results from the Phase II RESONATE -17 Trial

Picture3By Dr. Richard Furman, MD

Patients with chronic lymphocytic leukemia (CLL) with deletion of the short arm of chromosome 17 (del 17p) follow an aggressive clinical course and demonstrate a median survival of less than 2 years. Ibrutinib is a first-in-class inhibitor of Bruton’s tyrosine kinase (BTK), currently approved as treatment for CLL patients relapsed after one prior therapy or patients with del 17p at any line of therapy. Ibrutinib’s initial approval was based upon phase II data published in June 2013. The expanded approval is based upon results from the RESONATE trial comparing ibrutinib to ofatumumab.

At the 56th annual meeting of the American Society of Hematology (ASH), investigators presented the results of the phase II RESONATE -17 (PCYC-1117-CA) study investigating ibrutinib in relapsed CLL patients with deletion of 17p.

The study was designed to evaluate the efficacy and safety of single-agent ibrutinib as treatment of patients with relapsed or refractory CLL with del 17p or small lymphocytic leukemia (SLL). 144 patients (137 CLL patients, 7 SLL patients)  were enrolled and received ibrutinib 420 mg once daily until progression. The primary endpoint was overall response rate (ORR), with secondary endpoints including duration of response (DOR), progression-free survival (PFS), and safety of ibrutinib.

At a median follow up of 13 months, the median PFS and DOR had not been reached. At 12 months, 79.3% of patients were alive and progression-free, and 88.3% of responders were progression-free, with only 20 patients (13.9%) reporting progressive disease. At the time of data cut, the median treatment duration was 11.1 months, and 101 of 144 patients (70%) continued treatment with ibrutinib.

Efficacy results were consistent with earlier results, and the PFS compares favorably to that of treatment-naïve del 17p CLL patients receiving FCR or alemtuzumab. These results support ibrutinib as an effective therapy for patients with del 17p CLL/SLL.

Second Interim Analysis of Idelalisib and Rituximab for Patients with Relapsed CLL Confirms Previous Findings

Picture3By Dr. Richard Furman, MD

There is high unmet need for treatment of unfit patients with relapsed CLL, particularly in those characterized by adverse prognostic factors including del (17p) and/or TP53 mutations. Idelalisib is a first-in-class, targeted, highly selective, oral inhibitor of PI3 Kinase-delta enzyme recently approved for the treatment of relapsed CLL in combination with rituximab. During the 56th annual meeting of the American Society of Hematology (ASH) updated results were presented from a phase III study evaluating idelalisib in combination with rituximab in patients with relapsed CLL.

This study tested the efficacy of idelalisib in combination with rituximab compared to placebo with rituximab in patients with relapsed and refractory CLL who were considered unfit to receive cytotoxic therapy due to comorbidities, poor kidney function, or myelosuppression. 220 randomized patients (110 per group) received idelalisib + rituximab or a placebo + rituximab.  At progression, patients were given the option of enrolling in an extension study where they would receive idelalisib.  The primary endpoint was progression free survival.

At the first interim analysis, the results supported a marked improvement for patients who received idelalisib + rituximab compared with placebo + rituximab, with the median PFS not reached for patients taking idelalisib + rituximab compared with  5.5 months for patients taking the placebo. At 12 months, PFS rates for patients on idelalisib + rituximab was 66% compared to 13% for placebo + rituximab. The benefit favoring idelalisib + rituximab was seen in all risk‑groups. At the time of this analysis, 19 total deaths had occurred on the primary study: 6 on idelalisib + rituximab and 13 on placebo + rituximab.

For patients unfit to receive chemotherapy with relapsed CLL, idelalisib + rituximab demonstrated significant improvement over placebo + rituximab in terms of PFS, ORR, and OS with an acceptable safety profile. These results confirm the 1st interim analysis of the study.