Prophylactic cryotherapy for 2 hours prior to high-dose melphalan before autologous hematopoietic stem cell transplantation (HSCT) was as effective as 7 hours of cryotherapy in preventing grade 3 or 4 oral mucositis in patients with multiple myeloma. These results from a randomized, controlled phase 3 trial was published in Bone Marrow Transplantation.  

The approach cools the oral mucosa and is considered to be the standard-of-care treatment for the prevention of oral mucositis in patients with multiple myeloma who are receiving high-dose melphalan prior to autologous HSCT. Based on the design of earlier studies on this approach, cryotherapy is typically administration for 7 hours; however, this duration of cryotherapy delivery has been associated with patient discomfort that can negatively affect patient adherence.

In this study, cryotherapy was initiated 30 minutes prior to a single high dose of melphalan in all patients. Patients were randomly assigned 1:1 to another 1.5 hours of cryotherapy or another 6.5 hours of cryotherapy. The primary end point of the study was noninferiority in the incidence of grade 3 or grade 4 oral mucositis according to World Health Organization (WHO) criteria.

Of the 94 patients included in the primary analysis, 48 and 46 patients underwent cryotherapy for 2 and 7 hours, respectively.  There were no significant differences in the baseline characteristics of the 2 study arms. Rates of grade 3 or grade 4 oral mucositis were 2.1% and 4.3% in the 2-hour and 7-hour cryotherapy arms, respectively (95% CI, –0.09 to 0.049; =.98). Interestingly, all patients in the 2-hour arm completed cryotherapy, whereas 7 of those in the 7-hour arm discontinued cryotherapy early.

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In addition to concluding that 2-hour cryotherapy is equally as effective as 7-hour cryotherapy in preventing oral mucositis in patients with myeloma receiving high-dose melphalan before autologous HSCT, the authors also noted that “the true probability of moderate-to-severe oral mucositis with cryotherapy should rather be around 5%” and a significant number of patients did not develop mucositis at all.

Reference

Johansson JE, Bratel J, Hardling M, Heikki L, Mellqvist UH, Hasséus B. Cryotherapy as prophylaxis against oral mucositis after high-dose melphalan and autologous stem cell transplantation for myeloma: a randomized, open-label, phase 3, non-inferiority trial[published online February 4, 2019]. Bone Marrow Transplant. doi: 10.1038/s41409-019-0468-6