Combined Use of Multi-Day Doses of Palonosetron and Aprepitant with Low Dose Dexamethasone In Prevention of Nausea and Emesis Among Patients with Multiple Myeloma and Lymphoma Undergoing Autologous Hematopoietic Stem Cell Transplant (ASCT): A Pilot Study
Authors: Deauna-Limayo Delva , Aljitawi Omar , Ganguly Siddhartha , Abhyankar Sunil , Wick Jo , McGuirk Joseph 
Published: October 2019

Abstract
Abstract 1335
High dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) is a standard of care therapy patients with multiple myeloma and relapsed/refractory lymphomas. Unfortunately, high dose chemotherapy used in the preparative regimen is considered highly emetogenic. In one study, only 20% of patients undergoing ASCT managed to remain emesis-free. The 5-HT3 receptor antagonist is considered the backbone of anti-emetic regimens in this setting. Despite the combined use of these agents with dexamethasone, only 47% of recipients would achieve emetic control. Palonosetron, a second generation 5-HT3 antagonist, is approved as a single 0.25 mg IV dose in prevention of acute emesis in highly emetogenic chemotherapy regimens. Aprepitant represents a new class of oral anti-emetic which targets the NK-1 receptor. It is effective for both acute and delayed onset emesis.

Objectives and Methods:
Patients undergoing ASCT for multiple myeloma (MM) and relapsed lymphoma at the University of Kansas Medical Center were offered this study. The primary objective was to assess emetic responses to prophylactic multi-day doses of palonosetron, aprepitant and low dose dexamethasone. Emetic responses were assessed by daily patient diaries and the Multinational Association for Supportive Care in Cancer Antiemetic Tool (MAT). Nausea was measured using a Nausea Visual Score (NVS) of 0 to 10 with score of 0 having no nausea. A “modified” Osoba module was used to assess quality of life (QOL); and non-hematologic toxicities were evaluated. Preparative regimens were MEL140-200 for MM and BEAM or BEAC +/− rituximab for lymphomas. Standard doses aprepitant 125/80/80 mg were administered on days - 3, - 2, - 1 for MM group, and days - 7, - 6, - 5 for lymphoma group. Low dose dexamethasone 4 mg IV and multi-day doses of palonosetron 0.25 mg IV were administered on days - 3, - 2, -1, and on days - 7 thru - 3 for the MM and lymphoma groups, respectively. In both groups, palonosetron was repeated on day + 3. Acute chemotherapy-induced nausea/vomiting (CINV) was defined as nausea and/or vomiting within 24 hours of chemotherapy. Delayed CINV was defined as nausea and/or vomiting after 24 and up to 72 hours after chemotherapy; and extended CINV as nausea and/or vomiting after 72 hours of chemotherapy. Emetic responses were defined as follows: Complete Control (CC) – no emetic episode in 24 hours, no rescue medications and NVS of ≤ 2.5; Complete Emetic Response (CR) – 0 emetic episode, no rescue; Major Emetic Response (MR) – 1–2 episodes; Minor Emetic Response (MR) – 3–5 episodes; Failure - >5 episodes.

Results:
Between October 2007 and January 2010, 20 patients were enrolled, of which 18 were considered evaluable, 9 MM and 9 lymphoma – both Hodgkin's and non-Hodgkin's lymphoma. There were 11 males and 9 females. Median age was 55 (range: 35–66). All patients achieved at least a major emetic response in the acute, delayed and extended phases. Acute CINV responses were achieved in all patients: CC 2/9 (22%) and MR 7/9 (78%) in MM patients and CC 2/9 (22%), CR 2 (22%) and MR 5/9 (56%) in lymphoma patients. Delayed CINV responses were achieved in all patients: CC 2/9 (22%), CR 1 (11%) and MR 6/9 (67%) in MM patients and CC 4/9 (44%), CR 1 (11%) and MR 4/9 (44%) in lymphoma patients. Finally, all patients achieved extended CINV responses: CC 1/9 (11%) and MR 8/9 (89%) in MM patients and CC 2/9 (22%) and MR 7/9 (78%) in lymphoma patients. Eight patients developed grade 2–3 non-hematologic toxicities (arrhythmia, infection, febrile neutropenia, gastric mucositis, abdominal pain, and hyponatremia) attributed to the preparative transplant regimen. Only the arrhythmia was felt to be possibly related to the study drugs. Data on QOL will be presented during the conference.

Conclusion:
The combination of multi-day palonosetron combined with aprepitant and low dose dexamethasone appear to be well tolerated and effective in achieving at least a major emetic response in 100% of patients with MM and lymphoma undergoing high-dose therapy and ASCT. These encouraging results should warrant further evaluation in a larger population of ASCT patients.

Disclosures:
Deauna-Limayo: Eiasi: Research Funding. Aljitawi:Eisai: Research Funding.