Managing Patients Treated with Venetoclax Plus Rituximab for Relapsed/Refractory CLL

A multidisciplinary team approach may help in seeing optimal patient outcomes following the administration of a powerful drug combination for patients with relapsed/refractory chronic lymphocytic leukemia (CLL), according to a presentation at the Oncology Nursing Society 43^rd Annual Congress.

In April 2016, the FDA approved venetoclax (Venclexta), an oral inhibitor of the antiapoptotic protein B-cell lymphoma 2 (BCL-2) as a monotherapy for relapsed/refractory CLL.² The agent demonstrated complete response (CR) rates of 16—20%, including patients with high-risk chromosome 17p deletion. In addition, 24-month progression-free survival (PFS) was 49%.¹

In a phase Ib open-label, dose-escalation trial with 49 enrolled patients, venetoclax was combined with intravenous rituximab (Rituxin), a CD20 antibody, resulting in significant improvements compared with venetoclax alone.¹

Patients treated with venetoclax plus rituximab in the phase Ib study achieved a 51% CR rate, a 24-month PFS rate of 82%, and an ongoing response rate of 89%. The researchers noted they found indications that venetoclax can be discontinued once deep remission, defined as CR and/or minimal residual disease (MRD) negativity, has been achieved.¹

In the phase 1b study, patients were enrolled between August 6, 2012 and May 28, 2014. The median time on study was 44 months (range, 1 day-62 months). Twenty-six patients remain active on the study. As of July 2016, 18 patients with relapsed CLL who achieved a deep remission discontinued venetoclax and remained on study, and as of January 26, 2018, 16 of the patients still have MRD-negativity. Prior to discontinuing therapy, the median time on venetoclax was 16 months (range, 4.6-39.8 months).

In her presentation at the Congress, Peggy Alton, RN, BSN, OCN, CCRP, Duke University Medical Center, aimed to educate nurses about the management and care of patients during and following treatment with the venetoclax/rituximab combination.

Some key points for nurses who are administering the combination therapy to keep in mind include:

• Responses can be maintained after discontinuation of therapy when patients have achieved a deep response.
• Patients should be monitored for progression with a physical examination and absolute lymphocyte count.
• Nurses should discuss with patients the symptoms that are associated with progression, which include fever, fatigue, bruising, bleeding, night sweats, and weight loss.
• Evaluation for disease progression is merited if the presence of the aforementioned symptoms, as well as palpation of an enlarged lymph node, rising absolute lymphocyte count, or in some instances, a decrease in hemoglobin or platelets.

Alton also focused on the management of the patient, both during treatment and during the process of taking patients off the drugs.

“One of the best things we can do is to educate the patients and the caregivers about the things they need to be watching for, the neutropenia, the thrombocytopenia, the signs of possible tumor lysis which is often harder for them to tell clinically because that’s more about what’s happening with their labs, but certainly, making them aware to make sure they’re reporting everything to us,” she said.

For patients in the study, “their response to treatment came very fast. In terms of tumor lysis, and in the reduction of lymph nodes … patients could see a change within a week—if they were lymph nodes that they could see or feel in their neck … it was a pretty rapid response,” Alton said.

All patients experienced a treatment-emergent AE in this study. The most common treatment-emergent AEs of any grade among patients who discontinued venetoclax and remained on study included upper respiratory tract infection (67%), neutropenia (61%), and diarrhea (44%).

“When we started taking patients off venetoclax, we had to help patients understand that it was ok to stop treatments, and that we were going to monitor them very closely to make sure that if there’s evidence of disease progression, then obviously we would reevaluate and determine what needs to be done, or at what time point the treatment needs to be given.”

References

• Alton P, Brander D, Nandam R, Rodriguez K, Alter D. Management and care following treatment with venetoclax and rituximab for patients with relapsed chronic lymphocytic leukemia. Presented at: Oncology Nursing Society 43rd Annual Congress; May 17-20, 2018; Washington, DC. Poster-IS1. ons.confex.com/ons/2018/meetingapp.cgi/Paper/2792.
• FDA approves new drug for chronic lymphocytic leukemia in patients with a specific chromosomal abnormality. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm495253.htm. FDA website. Published online April 11, 2016. Accessed May 16, 2018.