Impact of concurrent gabapentin or pregabalin with high-dose melphalan in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplant.

BACKGROUND: Melphalan is an alkylating agent used in both autologous (ASCT) and allogeneic stem cell transplantation. It is a substrate of L-type amino acid transporter-1 (LAT-1) and LAT-2, which are involved in its tissue penetration and elimination. Gabapentin and pregabalin, common concomitant medications in patients with multiple myeloma undergoing ASCT, are also substrates of LAT transporters, raising concern for potential competitive inhibition of melphalan transport. We evaluated whether concurrent use of gabapentin or pregabalin in patients receiving high-dose melphalan (≥140 mg/m2 ) prior to ASCT impacted frequency and severity of melphalan-related adverse events. OBJECTIVE: We aimed to determine if concurrent administration of gabapentin or pregabalin and melphalan increased melphalan toxicity. METHODS: This was a single-center, retrospective evaluation including patients ≥18 years of age who received high-dose melphalan as part of a conditioning regimen at the Winship Cancer Institute of Emory University between August 1, 2010 and April 1, 2020 and were followed through their transplant admission. After identification and inclusion of patients who received melphalan in combination with gabapentin or pregabalin, patient matching based on age (±5 years), sex, and melphalan dose (140 mg/m2 or 200 mg/m2 ) was utilized to generate a comparable cohort of patients who received melphalan alone. The primary outcome was hospital length of stay (LOS); secondary outcomes included supportive care requirements between days +4 and day +14 and time to neutrophil and platelet-20 engraftment. RESULTS: Among 176 patients evaluated in each group, median hospital LOS was 16 days, median time to neutrophil engraftment was 14 days, and median time to platelet-20 engraftment was 16 days in both groups. In addition, there were no significant differences in supportive care requirements between groups. CONCLUSION: In this study, use of gabapentin or pregabalin in combination with melphalan did not impact safety of the conditioning regimen in patients undergoing ASCT.

Intranasal Ketamine and Its Potential Role in Cancer-Related Pain.

Cancer-related pain continues to be a significant therapeutic challenge, made more difficult by contemporary opioid use and diversion concerns. Conventional treatment using a tiered approach of nonsteroidal antiinflammatory drugs (NSAIDs), opioids, and adjuvant agents is limited; and alternatives are needed for patients with rapidly progressing pain and those who develop hyperalgesia and tolerance to opioids. Ketamine, an N-methyl-d-aspartate (NMDA) selective antagonist, has historically been used for anesthesia in adult and pediatric populations but has also been investigated for depression, bipolar disorder, and general and postoperative pain management. As an analgesic, low-dose ketamine decreases morphine requirements and rates of nausea and vomiting, suggesting a potentially beneficial role in cancer-related pain. Ketamine is typically administered intravenously and has a rapid onset of action with a relatively short half-life (2-3 hours) but is inconvenient for use in an ambulatory setting. Oral bioavailability is low and erratic, limiting application of this route for chronic use. Intranasal administration has a number of potential advantages, including avoidance of first-pass hepatic metabolism, no need for venous access, ability to repeat doses quickly, and rapid absorption. Although early studies of intranasal ketamine are promising in a number of indications, information is more limited in its use as an adjunct in cancer-related pain. We review the background, rationale, pharmacokinetics, and clinical and safety data using intranasal ketamine as an adjunctive agent and its potential in cancer-related pain.