Combination Therapy Active in Children, AYAs With Hodgkin Lymphoma

Brentuximab vedotin, a monoclonal antibody-drug conjugate, combined with gemcitabine may be a new treatment option for children and AYAs with relapsed or refractory Hodgkin lymphoma.

CHICAGO-Brentuximab vedotin, a monoclonal antibody-drug conjugate, combined with gemcitabine may be a new treatment option for children and adolescents and young adults (AYAs) with relapsed or refractory Hodgkin lymphoma.

Phase II data presented (abstract 7527) at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago suggest that brentuximab vedotin plus gemcitabine are a highly active combination for primary refractory or high-risk relapse of Hodgkin lymphoma and result in higher complete response rates.

In a Children’s Oncology Group study AHOD1221 (NCT01780662) with 42 patients, researchers at Roswell Park Cancer Institute found the complete response rate exceeded that seen after either brentuximab vedotin (34%) or gemcitabine (9%) alone. In addition, the study demonstrated that peripheral blood stem cells (PBSCs) can be collected successfully following this combination therapy thus making it an effective reinduction regimen in cases where autologous stem cell transplantation are indicated.

“The regimen is easily administered in the outpatient setting and is well tolerated, again an advantage over current retrieval regimens including ifosfamide and vinorelbine, or ifosfamide, cisplatin, and etoposide,” study investigator Kara Kelly, MD, who is an Endowed Chair of Pediatrics at Roswell Park Cancer Institute in Buffalo, told OncoTherapy Network.

Among the evaluable patients in the current phase II study, 23 (58%) achieved complete response to the combination within 4 cycles and six (15%) had a partial response. GCSF-stimulated PBSC collection was found to be successful in all 23 patients for whom it was attempted. Kelly said if these findings are confirmed in a phase III study, this combination might represent a new standard of care in this patient population.

Besides the high response rates, there are other benefits to this approach in terms of long-term side effects. “This regimen has the advantage that it does not include any alkylating agents, thus it does not contribute to long-term toxicities such as infertility and secondary leukemias-major concerns for this survivorship population, especially given that the success rate even in the relapse setting is favorable,” Kelly said.

In this current study, 42 patients were treated with this combination therapy and the median age was 17.4 years (range: 5.4–28.7 years). Among these patients, 55% were female and 83% had primary refractory disease or early relapse < 6 months after completion of primary treatment.

The most common adverse events included maculopapular rash (36% in cycle 1), neutropenia (33%), and elevated serum transaminases (21%). “The short-term side effects are very manageable. Bone marrow suppression was observed as expected, although less frequent than that observed with more myelosuppressive regimens,” said Kelly. “We monitored closely for pneumonitis, yet did not observe any cases attributable to the combination therapies. We envision that the greatest contribution is the reduction in risk for long-term toxicities given the side effect profile of these agents.”