Sivakumar Akhilesh, Bryson Evan B, Hall Kevin H, Maples Kathryn T, Goyal Subir, Joseph Nisha S, Hofmeister Craig C, Kaufman Jonathan L, Lonial Sagar, Nooka Ajay K, Harvey Robert Donald
Department of Pharmacy, Winship Cancer Institute of Emory University, Atlanta, Georgia, USA.
Department of Pharmacy, University of Kentucky Healthcare, Lexington, Kentucky, USA.
Pharmacotherapy. 2022 Mar;42(3):233-240. doi: 10.1002/phar.2667. Epub 2022 Feb 14.
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/m ) prior to ASCT impacted frequency and severity of melphalan-related adverse events.
We aimed to determine if concurrent administration of gabapentin or pregabalin and melphalan increased melphalan toxicity.
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/m or 200 mg/m ) 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.
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.
In this study, use of gabapentin or pregabalin in combination with melphalan did not impact safety of the conditioning regimen in patients undergoing ASCT.
美法仑是一种烷化剂，用于自体（ASCT）和异基因干细胞移植。它是L型氨基酸转运体-1（LAT-1）和LAT-2的底物，这两种转运体参与其组织渗透和消除过程。加巴喷丁和普瑞巴林是接受ASCT的多发性骨髓瘤患者常用的伴随用药，它们也是LAT转运体的底物，这引发了对美法仑转运潜在竞争性抑制的担忧。我们评估了在ASCT前接受大剂量美法仑（≥140mg/m²）的患者中同时使用加巴喷丁或普瑞巴林是否会影响美法仑相关不良事件的发生频率和严重程度。
我们旨在确定加巴喷丁或普瑞巴林与美法仑同时给药是否会增加美法仑毒性。
这是一项单中心回顾性评估，纳入了2010年8月1日至2020年4月1日期间在埃默里大学温希普癌症研究所接受大剂量美法仑作为预处理方案一部分、年龄≥18岁且在移植入院期间接受随访的患者。在识别并纳入接受美法仑联合加巴喷丁或普瑞巴林治疗的患者后，根据年龄（±5岁）、性别和美法仑剂量（140mg/m²或200mg/m²）进行患者匹配，以生成一组仅接受美法仑治疗的可比患者队列。主要结局是住院时间（LOS）；次要结局包括第+4天至第+14天的支持治疗需求以及中性粒细胞和血小板-20植入时间。
每组评估的176例患者中，两组的中位住院LOS均为16天，中位中性粒细胞植入时间均为14天，中位血小板-20植入时间均为16天。此外，两组之间的支持治疗需求无显著差异。
在本研究中，加巴喷丁或普瑞巴林与美法仑联合使用对接受ASCT患者的预处理方案安全性没有影响。
