Bendamustine and Bortezomib-Containing Regimens Produce Higher Response Rates and More Durable Responses Versus Cyclophosphamide-Based Therapy in Frontline Waldenstrom Macroglobulinemia Jorge J. Castillo, Joshua N. Gustine, Kirsten Meid, Toni E. Dubeau, Patricia Severns, Steven P. Treon Introduction Waldenstrom macroglobulinemia (WM) is Bing Center for Waldenstrom Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA an incurable IgM-secreting lymphoplasmacytic lymphoma. Primary Results (II) Results (III) therapy for symptomatic WM patients Results (I) Figure 1. PFS Benda-R, BDR, CDR Figure 3. OS Benda-R, BDR, CDR Conclusions often consists of combination therapy with Table. 1 Patients Characteristics
Log-rank p=0.10 Log-rank p=0.06 • Primary therapy with Benda-R, 1.00 an alkylating agent or proteasome 1.00 inhibitor with rituximab. However, Benda-R BDR CDR p- BDR, and CDR produces high
(n=57) (n=87) (n=38) value 0.75 randomized studies comparing these 0.75 response rates and durable PFS in Age >65 years 36 (63%) 32 (37%) 19 (50%) 0.01 treatment regimens are lacking in WM 0.50 patients with WM. Male sex 35 (61%) 53 (61%) 20 (53%) 0.64 0.50 patients. probabilityPFS
OS probabilityOS • The risk of progression is lower in 0.25 Benda-R BDR Hemoglobin ≤11.5 g/dl 23 (40%) 27 (31%) 10 (26%) 0.32 0.25 CDR patients treated with Benda-R
Methods Platelets ≤100 K/ul 9 (16%) 7 (8%) 2 (5%) 0.20 0.00 Benda-R BDR CDR 0 2 4 6 8 10 0.00 and BDR when compared to CDR. • We retrospectively searched our Years from treatment initiation 0 2 4 6 8 10 Serum B2M >3 mg/l 39 (64%) 43 (49%) 16 (42%) 0.02 Number at risk Years from treatment initiation • There is a trend towards a better database for WM patients who received Benda-R 57 32 12 3 0 0 Number at risk IgM >4,000 mg/dl 21 (37%) 62 (71%) 15 (39%) <0.001 BDR 85 54 27 12 4 0 Benda-R 57 33 13 5 0 0 OS in patients treated with BDR primary therapy with bendamustine- CDR 38 27 19 9 4 0 BDR 85 70 39 27 17 2 Marrow ≥50% 33 (58%) 38 (45%) 17 (45%) 0.29 CDR 38 30 22 12 8 1 rituximab (Benda-R), bortezomib- versus CDR. dexamethasone-rituximab (BDR), or Lymphadenopathy 25 (44%) 15 (17%) 14 (37%) 0.001 Figure 2. PFS maintenance R Figure 4. OS maintenance R • Maintenance rituximab is Splenomegaly 18 (32%) 6 (7%) 2 (5%) <0.001
cyclophosphamide-dexamethasone- Log-rank p<0.001 associated with both major and
1.00 1.00 rituximab (CDR) between 2005 and MYD88 L265P mutation 17 (89%) 23 (88%) 13 (100%) 0.60 deep responses to therapy as well
2016. 0.75 CXCR4 mutations 10 (53%) 11 (42%) 7 (54%) 0.71 0.75 as superior PFS and OS. • Pertinent clinical data were collected.
IPSSWM Log-rank p=0.03 0.50
• Response was assessed based on current 0.50
Low risk 20 (35%) 45 (52%) 24 (63%) 0.006 probabilityPFS
criteria. probabilityOS 0.25
• Univariate and multivariate regression Intermediate risk 17 (30%) 30 (35%) 7 (18%) No maintenance 0.25 Maintenance
models were fitted to evaluate the High risk 20 (35%) 11 (13%) 7 (18%) 0.00 No maintenance Maintenance association between clinical variables 0 2 4 6 8 10 0.00 Best response Years from treatment initiation 0 2 4 6 8 10 and response. Number at risk Years from treatment initiation No maintenance 64 24 8 1 0 0 Number at risk Disclosures: • Time to events was estimated using the Complete response 11 (19%) 9 (11%) 2 (5%) 0.37 Maintenance 116 89 50 23 8 0 No maintenance 64 40 19 10 6 2 Maintenance 116 93 55 34 19 1 Castillo: Very good PR 14 (26%) 20 (24%) 14 (37%) Kaplan-Meier method. Pharmacyclics: Consultancy, Research • The Cox regression method was used to PFS MVA HR 95% CI P-value Partial response 28 (49%) 40 (48%) 16 (42%) OS MVA HR 95% CI P-value Millennium: Research Funding fit univariate and multivariate models Minor response 2 (4%) 6 (7%) 2 (5%) Benda-R 0.2 0.1-0.5 <0.001 for progression-free (PFS) and overall BDR 0.2 0.04-0.6 0.006 Abbvie: Research Funding No response 2 (4%) 8 (10%) 4 (11%) BDR 0.6 0.3-1.0 0.05 survival (OS). Maintenance R 0.2 0.05-0.6 0.006 Janssen: Consultancy, Research • P<0.05 was considered statistically Received maintenance 35 (61%) 55 (65%) 26 (68%) 0.79 Maintenance R 0.1 0.06-0.2 <0.001 Treon: significant. Pharmacyclics: Consultancy, Research