Patients with low tumor burden as defined by ISS stages I and II at start of treatment appeared to gain increased benefit compared to those with stage III disease, confirming our previous observation (Danhof et al

Patients with low tumor burden as defined by ISS stages I and II at start of treatment appeared to gain increased benefit compared to those with stage III disease, confirming our previous observation (Danhof et al. treatment cycles. Median PFS was 6.4?months with 12-month and 18-month PFS rates of 35% and 28%, respectively. The overall response rate was 50% and 64% of responding AGN-242428 patients who achieved a longer PFS with elo/pom/dex compared to their most recent line of therapy. Objective responses were also seen in five patients who had been pretreated with pomalidomide. Low tumor burden was associated with improved PFS (13.5?months for patients with ISS stage I/II at study entry v 6.4?months for ISS III), although this difference did not reach statistical significance. No infusion-related reactions were reported. The most frequent grade 3/4 adverse events were neutropenia and pneumonia. Conclusion Elo/pom/dex is an active and well-tolerated regimen in highly advanced MM even after pretreatment with pomalidomide. (%)?del17p, t(4;14), or t(14;16)??Yes4 (18)??No15 (68)??Data not available?1q213 (14)??Yes2 (9)??No16 (73)??Data not available4 (18)Primary refractory to first line treatment, em n /em (%)7 (32)Median No. of previous treatment regimens (range)5 (1C16)Median time since initial diagnosis (range), years6.7 (0.3C11.7)Prior autologous stem cell transplantation, em n /em (%)17 (77)Prior allogeneic stem cell transplantation, em n /em (%)1 (4)Prior pomalidomide, em n /em (%)15 (68)Prior carfilzomib, em n /em (%)5 (23)Prior daratumumab, em n /em (%)2 (9)Refractory to most recent line of therapy, em n /em (%)13 (59)Refractory to lenalidomide, em n /em (%)13 (59) Open in a separate window Treatment exposure At database lock all patients had discontinued treatment, with disease progression as the most common reason. Only one patient discontinued early due to side effects. Two patients requested to stop IV treatment with elotuzumab after 6 and 10 cycles of the triplet combination, respectively, and continued on pom/dex. Another two patients went on to receive an autologous stem cell transplantation as a means of consolidation. The median number of treatment cycles was 5 (range 1C30). Efficacy All 22 patients were evaluable for response. 11 patients achieved a partial response (PR), yielding an Rabbit Polyclonal to Caspase 7 (p20, Cleaved-Ala24) overall response rate of 50%. Of note, five of these patients had been primary refractory to their first line regimen. The median PFS was 6.4?months. In a landmark analysis, 35% and 28% of patients were progression-free at 12?months and 18?months, respectively (Figs. ?(Figs.1,1, ?,2).2). Patients with high-risk cytogenetics had identical PFS compared to those with standard-risk disease (6.5 v 6.4?months, em p /em ?=?0.77). There was a clear trend for shorter PFS in patients with ISS stage III at study entry compared to those with stage I and II disease (6.5 vs. 13.5?months), AGN-242428 which did not reach statistical significance due to small sample size. Open in a separate window Fig. 1 Progression-free (dashed line) and overall survival (solid line) with elotuzumab, pomalidomide, and dexamethasone. PFS and OS rates at 12 and 18?months from start of treatment are displayed Open in a separate window Fig. 2 Progression-free survival with elotuzumab/pomalidomide/dexamethasone according to a response to prior lenalidomide, b prior exposure tp pomalidomide and c number of prior lines of therapy Patients refractory to lenalidomide showed no difference in their PFS compared to non-refractory patients ( em p /em ?=?0.98, Fig.?2a). Among patients who had previously received pomalidomide, 5 (33%) responded and another 3 (20%) had stable disease with most responses seen in patients who had pomalidomide immediately prior to elo/pom/dex (4 PR, 2 SD). Median PFS in pomalidomide-exposed patients was identical to that seen in pom-na?ve patients ( em p /em ?=?0.90, Fig.?2b). When elo/pom/dex was given directly after a pomalidomide-containing regimen (e.g., carfilzomib/pom/dex, bortezomib/doxorubicin/pom/dex), an absolute AGN-242428 gain in PFS of 4.3?months ( em p /em ?=?0.192) was seen when compared to patients with a regimen that did not include pomalidomide in the preceding line. Responses were also observed in 3 out of 5 patients who had been pretreated with a carfilzomib-based regimen; PFS did not differ significantly when compared to carfilzomib-na?ve subjects. At database lock, 14 of 22 patients (64%) had achieved a longer PFS to elo/pom/dex when compared to their most recent line of therapy. PFS did not differ in intensely pretreated ( ?4 prior therapies) versus less heavily pretreated patients ( em p /em ?=?0.99, Fig.?2c). The median follow-up for the study population was 42.5?months. The median overall survival (95% CI) was not reached (23.6?monthsnot estimable). At 12?months, 82% of patients ( em n /em ?=?18) were still alive; the 18-month OS rate was 73% (Fig.?1). In total, 17 of 21 patients (81%) received subsequent systemic therapy. One patient was lost to follow-up after discontinuation of elo/pom/dex. Two thirds of patients were treated with a daratumumab-containing regimen ( em n /em ?=?14); median exposure to the anti-CD38 antibody was 13.5?months. 4 patients underwent a salvage autologous.