Clinical Outcomes Related to the Use of Bendamustine Therapy for Multiple Myeloma Patients Relapsed/Refractory to Immunomodulatory Drugs and Proteasome Inhibitors

Turk J Haematol. 2017 Aug 2;34(3):233-238. doi: 10.4274/tjh.2016.0397. Epub 2017 Mar 8.

Abstract

Objective: Multiple myeloma patients who are relapsed or refractory to both proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) have been reported to have poor outcomes. Bendamustine has been reported to have an antitumor effect in newly diagnosed as well as relapsed/refractory multiple myeloma (RRMM). The aim of this retrospective study was to evaluate the efficacy of bendamustine therapy in heavily pretreated MM patients who were refractory to PIs and IMiDs.

Materials and methods: Nineteen RRMM patients treated either with bendamustine and steroids (n=13) or a combination of bendamustine with novel drugs (n=6) were included. The median number of previous treatment lines was 5 (minimum-maximum: 3-8) and median time from diagnosis was 6 years (minimum-maximum: 1-16). All of the patients were resistant to at least one of the IMiDs and one of the PIs. Bendamustine was given at doses ranging from 90 mg/m2 to 120 mg/m2 on days 1 and 2 of 28-day cycles.

Results: A median of 2 (minimum-maximum: 1-8) treatment cycles was administered per patient. The toxicity of bendamustine was mild and mostly of hematological origin. No complete remission was achieved. There was partial remission and stable disease in 21% and 11% of the patients, respectively. Sixty-eight percent of patients had progressive disease. The median progression-free survival and overall survival was 2 and 4 months, respectively.

Conclusion: Bendamustine therapy was well tolerated but showed limited anti-myeloma activity in heavily pretreated patients who were refractory to IMiDs and PIs.

Amaç: Proteazom inhibitörleri (PIs) ve immünomodülatuvar ilaçlar (IMiDs) içeren tedavi rejimlerine relaps refrakter multipl miyelom (RRMM) hastalarının prognozu oldukça kötüdür. Bendamustin yeni tanı almış ve RRMM hastalarında etkinliği bildirilmiş bir ajandır. Bu retrospektif çalışmanın amacı, öncesinde yoğun tedavi almış, PIs ve IMiDs tedavilerine RRMM hastalarında bendamustin tedavi etkinliğinin ortaya konmasıdır. Gereç ve Yöntemler: On dokuz RRMM hastasına bendamustin steroid (n=13) veya diğer ajanlarla kombine (n=6) edilerek verildi. Hastaların bendamustin tedavisi öncesi almış oldukları ortanca tedavi sayısı 5 (minimum-maksimum: 3-8), MM tanısından itibaren geçen zaman ortanca 6 yıl (minimum-maksimum: 1-16) olarak tespit edildi. Çalışmaya dahil edilmiş tüm hastalar en az bir IMiDs ve bir PIs dirençli idi. Bendamustin 90 mg/m2-120 mg/m2 dozlarında 28 günlük tedavi sikluslarının 1. ve 2. günlerinde verildi. Bulgular: Hastalar ortanca 2 (minimum-maksimum: 1-8) siklüs tedavi aldı. Bendamustin kaynaklı toksisite hafif ve genel olarak hematolojik orjinli tespit edildi. Hiçbir hastada tam remisyona elde edilemedi. Hastaların %21 ve %11’inde sırası ile kısmi remisyon ve stabil hastalık safhasına ulaşıldı. Hastaların %68’inde hastalık progresyonu saptandı. Ortanca progresyonsuz sağkalım ve genel sağkalım sırası ile 2 ve 4 ay olarak tespit edildi. Sonuç: IMiDs ve PIs dirençli hastalarda bendamustin tedavisi iyi tolere edilmesine rağmen kısıtlı anti-miyelom aktivitesi göstermiştir.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bendamustine Hydrochloride / administration & dosage*
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality*
  • Proteasome Inhibitors / administration & dosage*
  • Recurrence
  • Retrospective Studies
  • Survival Rate

Substances

  • Proteasome Inhibitors
  • Bendamustine Hydrochloride