Citations

8049 Background: The treatment paradigm of Waldenström macroglobulinemia (WM) continues to evolve as new therapies expand our options for this indolent and incurable disease. While more profound responses are generally associated with longer treatment-free intervals, the impact of depth of response from fixed duration therapy in WM patients' survival needs further evaluation. In this international, multicenter cohort study, we report the prognostic impact of depth of response in WM. Methods: 319 WM patients treated with frontline fixed duration therapy [Dexamethasone/Rituximab/Cyclophosphamide (DRC), Bendamustine/Rituximab (BR), or Bortezomib/Dexamethasone/Rituximab (BDR)] were included. Response at the completion of therapy (6 months) was used in a landmark analysis for progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) (defined as time from 6 months post treatment response to event or censor). Response was defined by modified IWWM-6 criteria. Associations between clinical variables and outcomes were evaluated using Cox proportional-hazard models. Results: The median age at the time of treatment initiation was 64 years (range: 29-94), 59% were men, and risk category by International Prognostic Scoring System (IPSS)-WM was low (n=67, 23%), intermediate (n=83, 29%), and high-risk (n=141, 48%). Evaluable responses at 6 months from frontline therapy [DRC (n=105; 41%), BR (n=83; 32%), BDR (n=68; 27%)] were available in 256 patients and included in the landmark analysis. Median follow-up was 63 months (95% CI: 59-70). The rate of major response (PR or better) at 6 months was 74% for the entire cohort. Five-year PFS rates from completion of therapy for patients who attained major response vs. those who did not were 71% and 43%, respectively (p<0.001). Five-year TTNT rates for patients who attained major response vs. not were 84% and 54%, respectively (p<0.001). Five-year OS rates for patients who attained major response vs. not were 92% and 77%, respectively (p<0.001). In multivariable analyses including other WM prognostic factors evaluated at initiation of frontline therapy, attaining a major response at 6 months was associated with superior PFS (HR 0.33, p<0.001), TTNT (HR 0.23, p<0.001), and OS (HR 0.31, p=0.001–Table). Conclusions: Achieving a major response at 6 months after frontline chemoimmunotherapy emerges as a significant prognostic factor for PFS, TTNT and OS in patients with WM.[Table: see text]

e19552 Background: Leukemic involvement (LI) in diffuse large B cell lymphoma (L-DLBCL) is very rare and has been sparsely reported. We report our experience with this entity in a large academic multi-center setting. Methods: Medical records of patients with DLBCL who received care at Mayo Clinic between 1/2003 and 6/2020 were reviewed. DLBCL patients with LI were identified. LI was defined as increased white blood cell counts and the presence of clonal B cells on peripheral blood flow-cytometry. Kaplan-Meier method was used for survival analysis. Results: Twenty patients with L-DLBCL were identified with a median follow-up of 32.5 months (CI95%, 32.5-NR). Median age at initial diagnosis was 62 (45-80) years. 60% (12/20) were male; 90% (18/20) were Caucasian. Pathologically, 90% (18/20) had DLBCL and 10% (2/20) had high-grade B cell lymphoma (HGBCL) with intermediate features between DLBCL and Burkitt lymphoma. By Hans criteria, 58% (11/19) had germinal center B-cell DLBCL (GCB-DLBCL) and 42% (8/19) had non-germinal center B-cell DLBCL (non-GCB-DLBCL). 40% (8/20) had transformed DLBCL (t-DLBCL); 36% (5/14) had double-hit lymphoma (DHL) by FISH analysis. LI was present in 55% (11/20) at initial diagnosis and 45% (9/20) at relapse. Median WBC was 39.5/ul (range, 4.3-121) with median absolute lymphocyte count of 25 k/ul (range, 0.7-117). Immunophenotypically, the leukemic lymphoma cells expressed CD19, CD20, and CD79a. Bone marrow involvement and pancytopenia were documented in all patients with a median bone marrow cellularity of 80%. Other extranodal sites of involvement with LI included spleen (65%;13/20), liver (20%;4/20), breast and soft tissue (20%;4/20), bladder or kidneys (10%;2/20), skeleton (10%;2/20), and myocardium (5%;1/20). 65% (13/20) had B-symptoms. All patients had LDH elevation (UNL 222 U/L) with a median of 2125 U/L (range, 308-10,760). 45% (5/11) of patients with LI at initial diagnosis had CNS involvement on relapse/progression. All patients with LI at initial diagnosis received anthracycline-based chemoimmunotherapy with or without CNS prophylaxis. Patients with LI at relapse had had a median of 2 prior treatments (range, 1-5) before LI. Median overall survival (OS) for the whole group was 9 months (CI 95%; 5.8-11.8). There were no long-term survivors. Median progression free survival after LI was 4.7 months (CI95%; 0.8-7.6) in the newly diagnosed group and 3 months (CI95%; 0.9-20) in the relapsed group. 90% (18/20) died due to their progressive disease. Cell of origin, DHL status, or newly diagnosed vs. relapsed status did not have a significant impact on OS in patients with L-DLBCL. Conclusions: Leukemic involvement at any time during the course of DLBCL is associated with poor prognosis. It also appears to be a major risk factor for CNS relapse. It is most frequently associated with DHL and t-DLBCL. Novel therapeutic approaches at the time of initial therapy need to be developed for L-DLBCL.

e19547 Background: Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is a rare, aggressive lymphoma characterized by skin involvement predominantly in the lower extremities, and is associated with an inferior prognosis compared to other primary cutaneous B-cell lymphomas. Immunochemotherapy with or without involved-field radiation therapy (IFRT) is considered standard, front-line therapy. Interestingly, over-expression of PD-L1/PD-L2 has been shown in a high proportion of PCDLBCL, LT cases, but efficacy of immune checkpoint inhibitors (ICI) in relapsed/refractory, PCDLBCL, LT has not been thoroughly studied. Therefore, we describe the outcomes of 1) immunochemotherapy with and without IFRT as front-line treatment of PCDLBCL, LT, and 2) ICIs in the relapsed/refractory setting. Methods: We conducted a retrospective cohort study of patients diagnosed with PCDLBCL, LT seen at Mayo Clinic from January 1, 2000 to December 31, 2020. Using the Kaplan-Meier method, we calculated progression-free survival (PFS), duration of response (DOR), and overall survival (OS) in patients who received front-line R-CHOP with and without IFRT, and salvage ICI therapy for relapsed/refractory disease. Results: A total of 28 patients with PCDLBCL, LT were identified. The median age at diagnosis was 71.6 years (range 48.0-91.7), 50% (N = 14) were male, and 78.6% (N = 22) had disease involvement of the lower extremities at diagnosis. For front-line treatment, 31.2% (N = 9) received R-CHOP with IFRT, and 31.2% (N = 9) received R-CHOP without IFRT. The median PFS in patients treated with R-CHOP plus IFRT was 41.8 months [95% CI: 30.2-69.6] compared to 13.7 months [95% CI: 10.7-27.7; p= 0.01] in those treated with R-CHOP without IFRT. The median OS in patients treated with R-CHOP plus IFRT was 74.7 months [95% CI: 53.0-108.6] compared to 38.2 months [95% CI: 26.0-80.4; p= 0.14] in those treated with R-CHOP without IFRT. Patient and disease characteristics were similar among these two groups. ICIs were used in 17.9% (N = 5) of patients with relapsed/refractory, PCDLBCL, LT, and these patients had received a median of three (range 2-10) prior systemic therapies. The overall response rate was 60% as three patients treated with ICIs achieved a complete response, and the other two patients showed no clinical response. The median DOR from ICIs was 23.0 months [95% CI: 3.6-26.0]. The median PFS from ICI therapy was 10.2 months [95% CI: 3.6 – not reached]. Only one of the five patients was noted to have a mild side effect from ICI treatment (elevated alkaline phosphatase, grade 1). Conclusions: R-CHOP with IFRT was associated with a longer median PFS compared to R-CHOP without IFRT as front-line therapy for PCDLBCL, LT. Furthermore, ICIs may have a role in treating relapsed/refractory disease as reasonable activity in heavily pre-treated patients and a favorable safety profile were observed in this study. Further studies would be of benefit to confirm our findings.