Activity with Thalidomide-Based Therapy Following Lenalidomide Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma.
Authors: Young Trieu , Chu Chia-Min , Xu Wei , Anglin Peter , Trudel Suzanne , Reece Donna E. , Chen Christine , Kukreti Vishal 
Published: October 2019

Abstract
Abstract 3855
Poster Board III-791
The optimal sequence of therapy in multiple myeloma (MM) remains unknown. Thalidomide (Thal) is the first immunomodulatory agent used for treating MM with anti-angiogenic properties and anti-inflammatory effects. Thereafter, Thal derived immunomodulatory compounds (IMiDs®) such as lenalidomide and pomalidomide were developed. These drugs are more potent than Thal with respect to stimulating T-cell proliferation and augmenting IL-2 and IFN-γ production. We know from previous MM clinical trials that lenalidomide is still effective after prior Thal exposure (Weber, Bloor 2007) but the use of Thal post lenalidomide based-therapy is unknown. At Princess Margaret Hospital (PMH), we have evaluated the use of Thal based therapy following treatment with lenalidomide plus dexamethasone (Len/Dex) for relapsed/refractory (rel/ref) disease. These patients were identified from PMH patients seen in the Expanded Access Program (MM016) and clinical trials for rel/ref disease. All patients were treated with Thal based treatment as the next therapy following progression on Len/Dex. Between December 2005 and May 2009, we identified 16 patients (10 males, 6 females); median age was 67 (range 44-83) years. With regards to previous therapy, 14 had undergone autologous stem cell transplantation (ASCT). Importantly, 4 patients had Thal induction therapy pre-ASCT for short duration of time at initial diagnosis while 12 patients had no prior Thal exposure. Before current Thal treatment, 3 patients had 2 prior lines of therapy, 5 had 3 prior lines of therapy; 4 had 4 prior lines of therapy and 4 with greater than 5 prior lines of therapy. With respect to immunoglobulin subtype, 6 were IgG, 7 with IgA and 3 with light chain disease only. At initial presentation, prognostic factors included a median β2m of 245 nmol/L, albumin of 39 g/L and creatinine of 88 μmol/L. Seven patients presented with ISS stage 1 disease, 7 with stage 2 and 2 with stage 3. With regards to Len/Dex therapy, the median duration of response was 8.7 months (range 1.4 to 45 months). The best haematological response to Len/Dex included CR for 1 patient, nCR for 3 patients, VGPR for 5 patients, PR for 5 patients and MR for 2 patients. Thereafter, Thal based therapy included steroids for 6 patients and alkylators with steroids in 10. The median follow up from start of Thal was 6.1 months (range 1.0 to 14.8). The median duration of Thal based therapy was 2.4 months (range 1.0 to 10.7). Best response to Thal based therapy was 3 (18%) PR, 4 (25%) MR and 7 (44%) with SD. Two patients had progressive disease. At time of analysis, only one patient remains on Thal with the rest having progressed on therapy. Only 4 patients remain alive at analysis.
In conclusion, the use of Thal based therapy post Len/Dex therapy results in a short median duration of response of 2.4 months with at best a partial response of 18% in this heavily treated population. Thalidomide maybe considered as a therapeutic option although this needs to be evaluated in a larger randomized study.

Disclosures:
Trudel: Celgene: Honoraria, Speakers Bureau; Ortho Biotech: Honoraria. Reece:Ortho Biotech: Honoraria, Research Funding. Chen:Celgene: Honoraria. Kukreti:Celgene: Honoraria.