Netupitant / palonosetron with dexamethasone for preventing nausea and vomiting in patients with multiple myeloma receiving high-dose melphalan for autologous hematopoietic stem cell transplantation: a single-center experience
https://doi.org/10.17650/1818-8346-2025-20-1-146-153
Abstract
Aim. To assess efficacy of netupitant / palonosetron with dexamethasone for chemotherapy‑induced nausea and vomiting in 20 patients with multiple myeloma who underwent autologous hematopoietic stem cell transplantation.
Materials and methods. The inclusion criteria were patients aged ≥18 years with a diagnosis of multiple myeloma, eligible for transplantation and a favorable response (according to the International Myeloma working Group criteria after induction therapy). Netupitant / palonosetron was administered at a dose of 1 capsule (300 mg netupitant; 0.5 mg palonosetron) 1 h before the start of chemotherapy conditioning (day –3) and dexamethasone was administered at day – 3 (12 mg), day – 2…0 (8 mg). Intravenous metoclopramide 10 mg was used as a rescue antiemetic when needed. Patients were evaluated every day for up to 12 days after autologous hematopoietic stem cell transplantation. The primary endpoint was the rate of complete response (no emesis and no rescue medication during 120 h after conditioning). Secondary endpoints were defined as the rate of complete response during the acute phase (0–24 h) and delayed phase (25–120 h) from the start of high‑dose melphalan. The safety of combination was also evaluated. 20 patients were included. The median age was 53.5 (37–67) years.
Results. Netupitant / palonosetron with dexamethasone prophylaxis showed a high efficacy in preventing chemotherapy‑induced nausea and vomiting during the high‑dose melphalan conditioning period. The primary outcome was largely achieved with a complete response observed in 14 (70 %) patients at 120 h. The complete response rate during the acute phase was 70 % (n = 14). during the delayed phase, the complete response rate was 95 % (n = 19). Grade 1 nausea and vomiting were experienced by 70 % of the patients, grade 2 – by 30 % of patients. No patients had grade 3–4 nausea or vomiting. Intravenous metoclopramide 10 mg was used in 30 % (6 patients).
Conclusion. Firstly in Russia we assess efficacy of netupitant / palonosetron with dexamethasone for chemotherapy‑induced nausea and vomiting in 20 patients with multiple myeloma who received high‑dose melphalan for autologous hematopoietic stem cell transplantation.
Keywords
About the Authors
N. E MochkinRussian Federation
Nikita Evgenievich Mochkin
105203; 70 Nizhnyaya Pervomayskaya St.; Moscow
N. S. Shorokhov
Russian Federation
105203; 70 Nizhnyaya Pervomayskaya St.; Moscow
V. O. Sarzhevskiy
Russian Federation
105203; 70 Nizhnyaya Pervomayskaya St.; Moscow
V. S. Bogatyrev
Russian Federation
105203; 70 Nizhnyaya Pervomayskaya St.; Moscow
A. A. Samoylova
Russian Federation
105203; 70 Nizhnyaya Pervomayskaya St.; Moscow
A. A. Rukavitsyn
Russian Federation
105203; 70 Nizhnyaya Pervomayskaya St.; Moscow
E. G. Smirnova
Russian Federation
105203; 70 Nizhnyaya Pervomayskaya St.; Moscow
A. E. Bannikova
Russian Federation
105203; 70 Nizhnyaya Pervomayskaya St.; Moscow
A. A. Mamedova
Russian Federation
105203; 70 Nizhnyaya Pervomayskaya St.; Moscow
Yu. V. Protopopova
Russian Federation
105203; 70 Nizhnyaya Pervomayskaya St.; Moscow
V. Ya. Melnichenko
Russian Federation
105203; 70 Nizhnyaya Pervomayskaya St.; Moscow
References
1. Child J., Morgan G., Davies F. et al. Highdose chemotherapy with hematopoietic stemcell rescue for multiple myeloma. N Engl J Med 2003;348(18):1875–83. DOI: 10.1056/NEJMoa022340
2. Larsen J., Nordström G., Ljungman P., Gardulf A. Symptom occurrence, symptom intensity, and symptom distress in patients undergoing highdose chemotherapy with stemcell transplantation. Cancer Nurs 2004;27(1):55–64. DOI: 10.1097/0000282020040100000007
3. López-Jiménez J., Martín-Ballesteros E., Sureda A. et al. Chemotherapyinduced nausea and vomiting in acute leukemia and stem cell transplant patients: results of a multicenter, observational study. Haematologica 2006;91(1):84–91.
4. Dranitsaris G., Molassiotis A., Clemons M. et al. The development of a prediction tool to identify cancer patients at high risk for chemotherapyinduced nausea and vomiting. Ann Oncol
5. ;28(6):1260–7. DOI: 10.1093/annonc/mdx100
6. Pastore D., Bruno B., Carluccio P. et al. Antiemetic prophylaxis in patients undergoing hematopoietic stem cell transplantation: a multicenter survey of the Gruppo Italiano Trapianto Midollo Osseo (GITMO) transplant programs. Ann Hematol 2020;99(6):867–75. DOI: 10.1007/s00277020039453
7. Navari R. Pathogenesisbased treatment of chemotherapyinduced nausea and vomiting – two new agents. J Support Oncol 2003;1(2):89–103.
8. Bayraktar U., Bashir Q., Qazilbash M. et al. Fifty years of melphalan use in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2013;19(4):344–56. DOI: 10.1016/j.bbmt.2012.08.011
9. D’Souza A., Fretham C., Lee S. et al. Current use of and trends in hematopoietic cell transplantation in the United States. Biol Blood Marrow Transplant 2020;26(10):e177–82. DOI: 10.1016/j.jtct.2021.02.006
10. Passweg J., Baldomero H., Chabannon C. et al. The EBMT activity survey on hematopoieticcell transplantation and cellular therapy 2018: CART’s come into focus. Bone Marrow Transplant
11. ;55(11):1604–13. DOI: 10.1038/s4140902008264
12. Giralt S. 200 mg/m2 melphalan – the gold standard for multiple myeloma. Nat Rev Clin Oncol 2010;7(8):490–1. DOI: 10.1038/nrclinonc.2010.104
13. Martino M., Olivieri A., Ofdani M. et al. Addressing the questions of tomorrow: melphalan and new combinations as conditioning regimens before autologous hematopoietic progenitor cell
14. transplantation in multiple myeloma. Expert Opin Investig Drugs 2013;22(6):619–34. DOI: 10.1517/13543784.2013.788643
15. Tendas A., Marchesi F., Mengarelli A. et al. Prevention of chemotherapyinduced nausea and vomiting after highdose melphalan and stem cell transplantation: review of the evidence and suggestions. Support Care Cancer 2019;27(4):793–803. DOI: 10.1007/s0052001845942
16. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Antiemesis. Version 2.2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf
17. Jordan K., Jahn F., Jahn P. et al. The NK1 receptorantagonist aprepitant in highdose chemotherapy (highdose melphalan and highdose TICE: paclitaxel, ifosfamide, carboplatin, etoposide): efficacy and safety of a triple antiemetic combination. Bone Marrow Transplant 2011;46(11):784–9. DOI: 10.1038/bmt.2010.205
18. Musso M., Scalone R., Crescimanno A. et al. Palonosetron and dexamethasone for prevention of nausea and vomiting in patients receiving highdose chemotherapy with autoSCT. Bone Marrow Transplant 2010;45(2):123–7. DOI: 10.1038/bmt.2009.114
19. Triflio S., Welles C., Seeger K. et al. Olanzapine reduces chemotherapyinduced nausea and vomiting compared with aprepitant in myeloma patients receiving highdose melphalan before stem cell transplantation: a retrospective study. Clin Lymphoma Myeloma Leuk 2017;17(7):584–9. DOI: 10.1038/bmt.2009.114
20. Bechtel T., McBride A., Crawford B. et al. Aprepitant for the control of delayed nausea and vomiting associated with the use of highdose melphalan for autologous peripheral blood stem cell transplants in patients with multiple myeloma: a phase II study. Support Care Cancer 2014;22(11):2911–6. DOI: 10.1007/s0052001422486
21. DeaunaLimayo D., Aljitawi O., Ganguly S. et al. Combined use of multiday palonosetron with aprepitant and lowdose dexamethasone in prevention of nausea and emesis among patients
22. with multiple myeloma and lymphoma undergoing autologous hematopoietic stem cell transplant: a pilot study. J Oncol Pharm Pract 2014;20(4):263–9. DOI: 10.1177/1078155213502103
23. Aapro M., Rugo H., Rossi G. et al. A randomized phase III study evaluating the efficacy and safety of NEPA, a fixeddose combination of netupitant and palonosetron, for prevention of chemotherapyinduced nausea and vomiting following moderately emetogenic chemotherapy. Ann Oncol 2014;25(8):1328–33. DOI: 10.1093/annonc/mdu101
24. Hesketh P., Rossi G., Rizzi G. et al. Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapyinduced nausea and vomiting following highly emetogenic chemotherapy: a randomized doseranging pivotal study. Ann Oncol 2014;25(7):1340–6. DOI: 10.1093/annonc/mdu110
25. Di Renzo N., Musso M., Scimè R. et al. Efficacy and safety of multiple doses of NEPA without dexamethasone in preventing nausea and vomiting induced by multipleday and highdose
26. chemotherapy in patients with non-Hodgkin’s lymphoma undergoing autologous hematopoietic stem cell transplantation: a phase IIa, multicenter study. Bone Marrow Transplant 2020;55(11):2114–20. DOI: 10.1038/s4140902009092
27. Apolito V., Giaccone L., Ferrero S. et al. Netupitantpalonosetron to prevent chemotherapyinduced nausea and vomiting in multiple myeloma patients receiving highdose melphalan and autologous stem cell transplantation. Ann Hematol 2020;99(12):2197–9. DOI: 10.1007/s00277020041806
28. Loteta B., Paviglianiti A., Naso V. et al. Netupitant/palonosetron without dexamethasone for preventing nausea and vomiting in patients with multiple myeloma receiving highdose melphalan
29. for autologous stem cell transplantation: a singlecenter experience. Support Care Cancer 2022;30:585–91. DOI: 10.1007/s00520021064727
30. Tendas A., Niscola P., Perrotti A. et al. Chemotherapy induced nausea and vomiting in bone marrow transplant: the unmet need. Support Care Cancer 2015;23(10):2211. DOI: 10.1007/s005200152711z
31. Tendas A., Sollazzo F., Bruno A. et al. Obstacles to managing chemotherapy-induced nausea and vomiting in highdose chemotherapy with stem cell transplant. Support Care Cancer
32. ;20(7):891–2. DOI: 10.1007/s0052001214111
33. Razvi Y., Chan S., McFarlane T. et al. ASCO, NCCN, MASCC/ESMO: a comparison of antiemetic guidelines for the treatment of chemotherapyinduced nausea and vomiting in adult patients. Support Care Cancer 2019;27(1):87–95. DOI: 10.1007/s005200184464y
34. Isoda A., Saito R., Komatsu F. et al. Palonosetron, aprepitant, and dexamethasone for prevention of nausea and vomiting after high-dose melphalan in autologous transplantation for multiple myeloma: a phase II study. Int J Hematol 2017;105(5):478–84. DOI: 10.1007/s1218501621526
35. Giralt S.A., Mangan K.F., Maziarz R.T. et al. Three palonosetron regimens to prevent CINV in myeloma patients receiving multiple-day highdose melphalan and hematopoietic stem cell transplantation. Ann Oncol 2011;22(6):939–46. DOI: 10.1093/annonc/mdq457
36. Mirabile A., Celio L., Magni M. et al. Evaluation of an everyother day palonosetron schedule to control emesis in multipleday high-dose chemotherapy. Future Oncol 2014;10(18):2569–78.
37. DOI: 10.2217/fon.14.132
38. Uchida M., Ikesue H., Miyamoto T. et al. Effectiveness and safety of antiemetic aprepitant in Japanese patients receiving highdose chemotherapy prior to autologous hematopoietic stem cell
39. transplantation. Biol Pharm Bull 2013;36(6):819–24. DOI: 10.1248/bpb.b1201012
40. Schmitt T., Goldschmidt H., Neben K. et al. Aprepitant, granisetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting after highdose melphalan in autologous transplantation for multiple myeloma: results of a randomized, placebocontrolled phase III trial. J Clin Oncol 2014;32(29):3413–20. DOI: 10.1200/JCO.2013.55.0095
41. Clark S., Clemmons A., Schaack L. et al. Fosaprepitant for the prevention of nausea and vomiting in patients receiving BEAM or highdose melphalan before autologous hematopoietic
42. stem cell transplant. J Oncol Pharm Pract 2016;22(5):416–22. DOI: 10.1177/1078155215585190
43. Gonullu G., Demircan S., Demirag M.K. et al. Electrocardiographic findings of palonosetron in cancer patients. Support Care Cancer 2012;20(10):1435–9. DOI: 10.1007/s0052001112265
44. Decramer M., Lacquet L.M., Fagard R., Rogiers P. Corticosteroids contribute to muscle weakness in chronic airflow obstruction. Am J Respir Crit Care Med 1994;150(1):11–6. DOI: 10.1164/ajrccm.150.1.8025735
45. Schakman O., Gilson H., Thissen J.P. Mechanisms of glucocorticoidinduced myopathy. J Endocrinol 2008;197(1):1–10. DOI: 10.1677/JOE070606
Review
For citations:
Mochkin N.E., Shorokhov N.S., Sarzhevskiy V.O., Bogatyrev V.S., Samoylova A.A., Rukavitsyn A.A., Smirnova E.G., Bannikova A.E., Mamedova A.A., Protopopova Yu.V., Melnichenko V.Ya. Netupitant / palonosetron with dexamethasone for preventing nausea and vomiting in patients with multiple myeloma receiving high-dose melphalan for autologous hematopoietic stem cell transplantation: a single-center experience. Oncohematology. 2025;20(1):146-153. (In Russ.) https://doi.org/10.17650/1818-8346-2025-20-1-146-153