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234 citation(s) found for "Ivana, Micallef".

Diffuse large B-cell lymphoma with leukemic involvement.
Ayala, Ernesto , Ansell, Stephen M. , Micallef, Ivana N. , Johnston, Patrick B. , Inwards, David J. , Kharfan‐Dabaja, Mohamed A. , Nowakowski, Grzegorz S. , Kuhlman, Justin J. , Moustafa, Muhamad Alhaj , Seegobin, Karan , Iqbal, Madiha , Rosenthal, Allison , Paludo, Jonas , Habermann, Thomas M. , Witzig, Thomas E. , Tun, Han W.

Journal of Clinical Oncology | June 2, 2021 | Volume: 39 | Issue: 15_suppl | Pages: e19552-e19552

10.1200/jco.2021.39.15_suppl.e19552 Get It

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.
Outcomes in primary cutaneous diffuse large B-cell lymphoma, leg type.
Kraft, Robert M. , Ansell, Stephen M. , Thanarajasingam, Gita , Inwards, David J. , Porrata, Luis F. , Micallef, Ivana N. , Thompson, Carrie A. , Johnston, Patrick B. , Nowakowski, Grzegorz S. , Villasboas, José C. , Bennani, N. Nora , Wang, Yucai , Habermann, Thomas M. , Witzig, Thomas E. , Lin, Yi , Paludo, Jonas

Journal of Clinical Oncology | June 2, 2021 | Volume: 39 | Issue: 15_suppl | Pages: e19547-e19547

10.1200/jco.2021.39.15_suppl.e19547 Get It

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.
Impact of time to relapse and response to salvage therapy on post autologous stem cell transplant outcomes in relapsed or refractory diffuse large B-cell lymphoma.
Maliske, Seth , Micallef, Ivana N. , Inwards, David J. , Porrata, Luis F. , Ansell, Stephen M. , Kharfan‐Dabaja, Mohamed A. , Nowakowski, Grzegorz S. , Johnston, Patrick B. , Tun, Aung M. , Wang, Yucai , Farooq, Umar , Rosenthal, Allison , Link, Brian K. , Villasboas, José C. , Paludo, Jonas , Cerhan, James R. , Habermann, Thomas M. , Witzig, Thomas E.

Journal of Clinical Oncology | June 2, 2021 | Volume: 39 | Issue: 15_suppl | Pages: e19501-e19501

10.1200/jco.2021.39.15_suppl.e19501 Get It

e19501 Background: The current standard of care for patients with relapsed or refractory (RR) diffuse large B-cell lymphoma (DLBCL) following frontline immunochemotherapy (IC) is salvage therapy, followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) rescue in patients responding to salvage therapy. Time to first relapse (or refractory status) and response to salvage therapy in patients with RR DLBCL may reflect the chemosensitivity of the underlying disease. The aim of this study is to determine whether these factors impact post-ASCT outcomes. Methods: Patients with DLBCL that relapsed after R-CHOP or R-CHOP-like frontline therapy who underwent salvage therapy and ASCT at Mayo Clinic or University of Iowa between 07/2000 and 4/2020 were identified from institutional lymphoma and transplant databases. Clinical characteristics, treatment information, and outcome data were abstracted. Progression-free survival (PFS) and overall survival (OS) from the time of ASCT were analyzed using Kaplan-Meier method and Cox proportional hazards models. Results: A total of 437 patients with RR DLBCL who underwent salvage therapy and ASCT were identified. 280 (64%) were male. Median time from initial diagnosis to 1st relapse/salvage was 1.0 years (range 0.1-16.4). A median of 1 line (range 1-3) of salvage therapy was required. Response prior to ASCT was complete response (CR) in 211 (48%), partial response in 199 (46%), stable disease in 24 (5%), and unknown in 3 (1%) patients. Median age at ASCT was 61 years (range 19-78), and median follow up after ASCT was 8.0 years (95% CI 7.2-8.7). Median PFS and OS was 2.7 (95% CI 1.5-4.3) and 5.4 (4.2-7.4) years, respectively. Time to 1st relapse/salvage (≤1 vs 1-2 vs > 2 years) was not associated with PFS (median 0.8 vs 2.4 vs 4.9 years, p = 0.170) but was associated with OS (2.4 vs 7.4 vs 6.8 years, p = 0.013). Patients who required > 1 line of salvage therapy had significantly inferior PFS (median 0.3 vs 4.5 years, p < 0.001) and OS (0.9 vs 7.4 years, p < 0.001). In addition, patients who failed to achieve a CR prior to ASCT had significantly worse PFS (median 0.8 vs 5.3 years, p < 0.001) and OS (2.7 vs 9.2 years, p < 0.001). In multivariate Cox regression models adjusted for age and sex, time to 1st relapse/salvage was not associated with PFS (p = 0.313) or OS (p = 0.081); however, lines of salvage and response prior to ASCT remain significantly prognostic for PFS ( > 1 line of salvage: HR 2.14, 95% CI 1.59-2.87, p < 0.001; non-CR: HR 1.61, 95% CI 1.26-2.05, p < 0.001) and OS ( > 1 line of salvage: HR 2.25, 95% CI 1.66-3.05, p < 0.001; non-CR: HR 1.63, 95% CI 1.26-2.12, p < 0.001). Conclusions: In patients with RR DLBCL following frontline IC, requiring more than 1 line of salvage therapy and failure to achieve CR are strong independent risk factors for poor PFS and OS after ASCT. Novel therapies such as CAR-T cell therapy should be studied in this population.
Survival trends of older adult patients with diffuse large B-cell lymphoma: A National Cancer Database analysis.
Andrade-Gonzalez, Xavier , Thanarajasingam, Gita , Thompson, Carrie A. , Johnston, Patrick B. , Micallef, Ivana N. , Porrata, Luis F. , Inwards, David J. , Ansell, Stephen M. , Nowakowski, Grzegorz S. , Saliba, Antoine N. , Fuentes, Harry E , Xie, Zhuoer , Habermann, Thomas M. , Villasboas, José C. , Paludo, Jonas , Lin, Yi , Bennani, N. Nora , Witzig, Thomas E. , Wang, Yucai

Journal of Clinical Oncology | June 2, 2021 | Volume: 39 | Issue: 15_suppl | Pages: 7542-7542

10.1200/jco.2021.39.15_suppl.7542 Get It

7542 Background: 60-70% of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) can be cured with R-CHOP or R-CHOP-like immunochemotherapy. However, patients ≥80 years of age were either excluded or underrepresented in modern DLBCL trials, and their outcomes are understudied. The aim of this study is to define the survival trends and risk factors for inferior survival in older adult patients with DLBCL. Methods: Patients with newly diagnosed DLBCL were identified from the National Cancer Database (2004-2017, representing the rituximab era). Clinical characteristics, treatment, and outcomes were compared between patients ages ≥ 80, 65-79, and < 65 years. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis. Results: A total of 231,756 patients with newly diagnosed DLBCL were identified; 46,250 (20%) were ≥80 years, 87,702 (38%) were 65-79 years, and 97,904 (42%) were < 65 years. Patients ≥80 years were more likely to have a higher Charlson-Deyo Comorbidity Index score (CDS) (CDS ≥2, 12% vs 11% vs 8%, p = 0.001), less likely to receive systemic chemotherapy (63% vs 83% vs 89%, p < 0.001), and more likely to receive treatment at a non-academic center (71% vs 65% vs 48%, p < 0.001), compared to patients 65-79 and < 65 years, respectively. Median overall survival (OS) was significantly worse for patients ≥80 years compared to patients 65-79 years (11.6 vs 61.0 months, p = 0.001) and patients < 65 years (11.6 vs 178.1 months, p = 0.001). During the study period, the median OS had only minimally improved for patients ≥80 years (10.6 months in 2004-2007 vs 11.5 months in 2008-2011 vs 12.3 months in 2012-2016, p = 0.006). In contrast, the OS improvement appears more meaningful in patients 65-79 years (median in months: 51 vs 61.2 vs 65.9, p = < 0.001) and patients < 65 years (median in years: 14.6 vs 11.3 vs not reached, p < 0.001) in the prespecified intervals (2004-07, 2008-11, and 2012-16). In multivariate analysis, the most substantial risk factor for worse survival in patients ≥80 years was not receiving systemic therapy (hazard ratio [HR] = 3.26, 95%CI = 3.01-3.54, p = 0.001). Other risk factors associated with worse survival included high-risk IPI score (HR = 2.16, 95%CI = 1.96-2.39, p = 0.001), CDS score ≥2 (HR = 1.56, 95%CI = 1.40-1.73, p = 0.001), male sex (HR = 1.16, 95%CI = 1.09-1.24, p = 0.001), B symptoms at diagnosis (HR = 1.16, 95%CI = 1.08-1.25, p = 0.001), and treatment at a non-academic center (HR = 1.1, 95%CI = 1.01-1.20, p = 0.001). Conclusions: Patients ≥ 80 years of age with DLBCL have a significantly inferior survival which has not meaningfully improved in recent years. More than 1/3 of patients ≥ 80 years did not receive systemic therapy. Older adult patients with DLBCL should be assessed for fitness for chemotherapy using validated geriatric assessment tools. Novel therapeutic strategies with favorable safety profiles are urgently needed for this expanding patient population.
Salvage therapies in transplant-eligible relapsed classic Hodgkin lymphoma, are novel regimens better?
Reeder, Craig B. , Inwards, David J. , Ayala, Ernesto , Nowakowski, Grzegorz S. , Porrata, Luis F. , Kharfan‐Dabaja, Mohamed A. , Johnston, Patrick B. , Ansell, Stephen M. , Micallef, Ivana N. , Desai, Sanjal H. , Wang, Yucai , Rosenthal, Allison , Tun, Han W. , Paludo, Jonas , Villasboas, José C. , Moustafa, Muhamad Alhaj , Habermann, Thomas M.

Journal of Clinical Oncology | June 2, 2021 | Volume: 39 | Issue: 15_suppl | Pages: 7530-7530

10.1200/jco.2021.39.15_suppl.7530 Get It

7530 Background: Clinical trials of novel salvage therapies (ST) have encouraging outcomes for relapsed/refractory classic Hodgkin lymphoma (R/R cHL) eligible for autologous stem cell transplant (ASCT). In this observational study, we report efficacies and outcomes of different ST in ASCT-eligible R/R cHL. Methods: Consecutive ASCT-eligible R/R cHL pts at 3 Mayo Clinic sites were included. Demographics and clinical variables at relapse were recorded by medical records review. Time to event endpoints were defined from relapse. Univariate associations were confirmed in multivariate models of age, sex, B symptoms, stage, bulky disease (BD, single mass > 6 cm) extra nodal disease (END), primary refractory disease (PRD) and early relapse (ER, within 1 year). Results: From Jan 2008 to May 2020, 207 ASCT-eligible pts with R/R cHL were included. Median age was 33 (24-43) years, 53% were male, 52% had advanced stage, 24% had BD, 36% had B symptoms, 41% had END, 11% had PRD and 43% had ER. All patients received ST and underwent ASCT; 43 (21%) received 2 ST, 14 (7%) 3 ST and 4 (0.5%) received 4 ST. 6 groups of ST were identified: ifosfamide, carboplatin and etoposide (ICE), bendamustine/brentuximab (BBV), brentuximab vedotin (BV), gemcitabine-based therapy (Gem), checkpoint inhibitor (CPI), and others. Table lists response to first line ST. BBV had significantly higher overall response rate (ORR) and complete response (CR) as first ST in univariate and multivariate models. 114 (79%) after ICE, 30 (97%) after BBV, 15 (56%) after BV, 25 (76%) after Gem, 8 (73%) after CPI and 15 (79%) after other ST underwent ASCT. Higher number of pts were bridged to ASCT after BBV than ICE (p<0.01). 110 (53%) went to ASCT in CR, 74 (36%) in partial response (PR) and 11% in progressive disease (PD). 43 received BV maintenance (BVm) after ASCT. Pts going to ASCT in PR or PD had significantly lower progression free survival (PFS) compared to pts in CR (2 yr PFS: 62%, 18% vs 77%, respectively, p<0.0001) in univariate and multivariate models. There was no difference in PFS and overall survival (OS) by type of ST. BVm was associated with higher PFS (HR 0.3 (CI95 0.2-0.8)) and higher number of ST was associated with lower OS (HR 2 (CI95 1.4-3)) in multivariate model (p<0.001). For pts transplanted in CR, there was no significant difference in PFS and OS by type of ST but higher number of ST predicted lower OS (HR 2.4 (CI95 1.2-3.5), p<0.01). Conclusions: Type of ST did not predict survival, response to and number of ST did. For pts with CR, number of ST not type of ST predicted survival. BBV had higher response rates, higher rates of bridge to ASCT, and may be a preferable ST than ICE. Large, randomized trials are needed to evaluate efficacy of BBV compared to ICE.[Table: see text]
Progression-free survival at 24 months as a landmark after autologous stem cell transplant in relapsed or refractory diffuse large B-cell lymphoma.
Maliske, Seth , Micallef, Ivana N. , Inwards, David J. , Porrata, Luis F. , Kharfan‐Dabaja, Mohamed A. , Orme, Jacob J. , Thompson, Carrie A. , Ansell, Stephen M. , Nowakowski, Grzegorz S. , Johnston, Patrick B. , Tun, Aung M. , Wang, Yucai , Maurer, Matthew J. , Rosenthal, Allison , Link, Brian K. , Cerhan, James R. , Habermann, Thomas M. , Witzig, Thomas E. , Farooq, Umar

Journal of Clinical Oncology | June 2, 2021 | Volume: 39 | Issue: 15_suppl | Pages: 7522-7522

10.1200/jco.2021.39.15_suppl.7522 Get It

7522 Background: Patients with newly diagnoseddiffuse large B-cell lymphoma (DLBCL) who achieve event-free survival at 24 months (EFS24) following immunochemotherapy (IC) have excellent overall survival (OS) similar to that of age- and sex-matched general population. The standard of care for patients with relapsed or refractory (RR) DLBCL following frontline IC is salvage therapy followed by autologous stem cell transplant (ASCT). The goal of this study is to evaluate the role of progression-free survival (PFS) at 24 months (PFS24) as a landmark after ASCT in patients with RR DLBCL. Methods: Patients with RR DLBCL after frontline R-CHOP or R-CHOP-like IC who underwent salvage therapy and ASCT at Mayo Clinic or University of Iowa between 07/2000 and 4/2020 were identified from institutional lymphoma transplant databases. Clinical characteristics, treatment information, and outcome data were abstracted. Post-ASCT PFS, OS, and post-relapse survival (PRS) were plotted by Kaplan-Meier method, and cumulative incidences of relapse vs non-relapse mortality (NRM) and different causes of death were compared accounting for competing events. Statistical analyses were performed in EZR v1.54. Results: A total of 437 patients were identified. Median age at ASCT was 61 years (range 19-78), and 280 (64%) were male. After a median post-ASCT follow up of 8.0 years (95% CI 7.2-8.7), 215 patients had a relapse (or disease progression), 180 within 2 years and 35 after 2 years. For the entire cohort, post-ASCT relapse rate was much higher than NRM rate (48.1 vs 9.1% at 5-year). Median PFS and OS after ASCT was 2.7 and 5.4 years, respectively. Lymphoma was the primary cause of death after ASCT. In contrast, for patients who had achieved PFS24 (n = 220), rates of post-PFS24 relapse and NRM were similar (14.8% and 12.3% at 5-year). Median PFS and OS after achieving PFS24 was 10.0 and 11.5 years, respectively. Lymphoma related and unrelated death rates were similar after achieving PFS24 (Table). For all patients who had a post-ASCT relapse, median PRS was 0.7 years (95% CI 0.5-0.9), and late relapse ( > 2 vs ≤2 years after ASCT) was associated with better PRS (median 2.3 [1.7-4.8] vs 0.5 [0.3-0.7] years, p < 0.001). Conclusions: Post-ASCT PFS24 is an important prognostic predictor of post-ASCT outcomes in patients with RR DLBCL following frontline IC.[Table: see text]
Outcomes in mantle cell lymphoma with central nervous system involvement.
McLaughlin, N , Inwards, David J. , Micallef, Ivana N. , Nowakowski, Grzegorz S. , Thanarajasingam, Gita , Porrata, Luis F. , Thompson, Carrie A. , Johnston, Patrick B. , Ansell, Stephen M. , Wang, Yucai , Villasboas, José C. , Habermann, Thomas M. , Witzig, Thomas E. , Lin, Yi , Bennani, N. Nora , Paludo, Jonas

Journal of Clinical Oncology | June 2, 2021 | Volume: 39 | Issue: 15_suppl | Pages: e19527-e19527

10.1200/jco.2021.39.15_suppl.e19527 Get It

e19527 Background: While extra nodal involvement by MCL is relatively common, involvement of the central nervous system (CNS) is a rare ( < 5% of cases) complication with limited treatment options. We report the outcomes of a large cohort of patients (pts) with CNS MCL. Methods: MCL pts with CNS involvement seen at Mayo Clinic between 1/1/1995-9/16/2020 were identified. CNS involvement was defined by histologically confirmed CNS MCL, CSF analysis demonstrating lymphoma cells, and/or neuroimaging findings compatible with CNS lymphoma. Medical records were reviewed for baseline characteristics, treatment, and outcome. Kaplan-Meier method was used for time to event analysis. Results: Out of 1,753 pts with MCL, 36 (2%) had CNS involvement by MCL. Median age at MCL diagnosis was 64 years (range 36-83) and 26 were male (72%). At MCL diagnosis, non-CNS extranodal involvement was seen in 30 pts, 24 with 1 site and 6 with ≥ 2 sites; 24 had bone marrow involvement. 11 (31%) pts had blastoid variant. Median Ki-67 was 40% (range 15-100%). MIPI score was available in 17 pts [low risk (n = 5, 29%), intermediate risk (n = 9, 53%), high risk (n = 3, 18%)]. The most common frontline regimen for MCL was R-CHOP and 14 (39%) pts underwent autologous stem cell transplant in CR1. The incidence of CNS involvement was overall similar over the study period. Median time from MCL diagnosis to CNS involvement was 25 months (m) (range 0-167). 4 (11%) pts presented with CNS involvement at initial diagnosis and 32 presented at relapse (12 isolated CNS relapse and 20 concurrent CNS and systemic relapse. Abnormal CSF was noted in 27 (87%) pts [consistent with MCL diagnosis (n = 26), atypical lymphocytes (n = 1)]. Abnormal CNS imaging was reported in 27 (75%) pts [leptomeningeal (n = 18), leptomeningeal and parenchymal (n = 5), parenchymal (n = 2), ocular (n = 2)]. First line CNS-directed therapy data was available in 33 (92%) pts. 12 (34%) received intrathecal (IT) therapy alone, 19 (54%) received systemic +/- IT therapy, 2 (6%) received radiation alone, and 2 (6%) pts received no treatment (hospice). The overall CNS response to therapy was CR in 13 (42%) pts, PR in 3 (10%), SD in 8 (26%), and PD in 7 (22%) pts. Three pts received BTK inhibitors [ibrutinib (n = 2) or acalabrutinib (n = 1)] as the first CNS-directed therapy. One patient achieved a CR with a response lasting 4 m, another patient achieved a PR with response lasting 10 m. CNS response data was not available in the remaining pts. Median follow up from CNS involvement was 72 m (95% CI: 41-NR). Median EFS for the 1 st CNS-directed therapy was 3.7 m (95% CI: 1.6-6.1). At last follow up, 30 pts were deceased. The cause of death was CNS lymphoma in 10 (33%) pts and systemic lymphoma in 9 (30%) pts. Median OS from CNS involvement was 4.7 m (95% CI: 2.3-6.7). Conclusions: CNS involvement by MCL has dismal outcomes as evident by a median OS of approximately 5 m. BTK inhibitors may have a role in treatment of this rare complication, but further prospective investigation is needed.
Clinical manifestations of, diagnostic approach to, and treatment of neurolymphomatosis in the rituximab era
Khurana, Arushi , Novo, Mattia , Nowakowski, Grzegorz S. , Ristow, Kay M., Spinner, Robert J. , King, Rebecca L. , Micallef, Ivana N. , Johnston, Patrick B. , Hunt, Christopher H. , Lachance, Daniel Honore , Habermann, Thomas M.

Blood Advances | March 4, 2021 | Volume: 5 | Issue: 5 | Pages: 1379-1387

10.1182/bloodadvances.2020003666 | PMID 33661298 Get It

AbstractNeurolymphomatosis (NL) is a rare manifestation of lymphoma, with limited evidence for optimal management. The largest patient series, 50 cases of lymphoma and leukemia, was published in 2010 with limited rituximab exposure. This study aims to evaluate the clinical presentation, diagnostic testing, and outcomes of NL in the rituximab era. Forty biopsy-proven cases of NL, in association with non-Hodgkin lymphoma (NHL), at the Mayo Clinic were retrospectively evaluated. B-cell NHL was associated with 97% of NL cases, of which diffuse large B-cell lymphoma (DLBCL) was the most common (68%). Primary NL, defined as neural involvement present at the time of diagnosis of lymphoma, was noted in 52% cases. Seventy percent of patients presented with sensorimotor weakness and neuropathic pain. Magnetic resonance imaging (MRI) was positive in 100% patients. Overall survival (OS) was significantly better for primary NL and NL associated with indolent lymphomas. Relapses were seen in 60% (24/40) of patients; 75% involved the peripheral or central nervous system at relapse. The use of rituximab in the frontline setting significantly impacted progression-free survival (PFS). Transplant consolidation was noted to be associated with improved OS. This study adds to the available literature on NL in the rituximab era. The overall outcomes have improved in recent years. In our experience, MRI and positron emission tomography/computed tomography may be required for accurate assessment of the extent of disease involvement and identification of an optimal biopsy site. The use of rituximab was associated with improvement in PFS, and autologous stem cell transplant was associated with OS.
Lines of Therapy before Autologous Stem Cell Transplant (ASCT) and CAR-T Infusion Affect Outcomes in Aggressive Non-Hodgkin's Lymphoma (NHL)
Khurana, Arushi , Hathcock, Matthew , Gandhi, Sangeetha, Truong, Tuan, Bennani, Nabila Nora, Ansell, Stephen M. , Inwards, David J. , Porrata, Luis F. , Johnston, Patrick B. , Micallef, Ivana N. , Habermann, Thomas M. , Saleh, Abdullah S. Al , Paludo, Jonas , Villasboas, José C. , Lin, Yi

Blood | February 6, 2021 | Volume: 136 | Issue: Supplement 1 | Pages: 29-30

10.1182/blood-2020-142511 Get It

Background: Anti CD-19 chimeric antigen receptor T-cell therapy (CAR-T) is approved to treat relapsed/refractory (R/R) aggressive NHL after 2 or more lines of therapy. Randomized clinical trials are ongoing comparing CAR-T and autologous stem cell transplant (ASCT) in second line. In standard of care practice, patients refractory to second line chemotherapy are sometimes treated with third line chemotherapy and taken to ASCT if disease is chemo-sensitive. Current study aims to evaluate the impact of prior lines of therapy on the efficacy of CAR-T and ASCT. Methods: A retrospective review of patients who received ASCT and/or axicabtagene ciloleucel (axi-cel) for R/R aggressive NHL from June 2016 - January 2020 at Mayo Clinic, Rochester was performed. The lymphoma types included in the study were DLBCL, transformed lymphoma (TFL), high grade B-cell lymphoma (HGBL), and primary mediastinal large B-cell lymphoma (PMBCL). Response to all lymphoma-directed therapy was evaluated using 2014 Lugano criteria. Overall survival (OS) was defined as time from CAR-T or ASCT infusion to death, and progression free survival (PFS) was defined as time from CAR-T or ASCT infusion to disease progression, or next treatment. Categorical data was analyzed as Chi-square or fishers exact test as appropriate. Continuous variables were analyzed using Wilcoxon Rank Sum test. Analysis was performed in R3.6.3. Results: A total of 105 patients underwent ASCT and 53 patients underwent CAR-T therapy in the study period with at least 6 months follow-up. Of the 105 ASCT patients, 87 received ASCT after 2 lines of chemotherapy, ASCT(2), and 18 received ASCT after 3 lines of chemotherapy, ASCT(3). Twenty six of the ASCT [n=19, ASCT(2) and n=7, ASCT(3)] patients received CART in subsequent therapy. Baseline characteristics were comparable between the two groups except ASCT(3) had higher percent of refractory disease after first line (table 1). With a median follow up of 17.4 months, the PFS was significantly longer for the ASCT(2) group with a trend toward longer OS (Figure 1; PFS @ 1 year: ASCT(2) 67%, 95%CI 58-79%; ASCT(3) 27%, 95%CI 27-74%; p = 0.036). Among the CAR-T recipients, only 18 (33%) patients received CAR-T in the earliest possible indication, CAR-T(2): after 2 lines of chemotherapy (n=12) and/or after ASCT(2) (n=6), table 1. Compared to patients who received CAR-T in later lines (CAR-T 3+), OS was significantly longer for patients who received CAR-T(2), with a trend toward longer PFS (Figure 1; OS @ 1 year: CAR-T (2) 82%, 95%CI 65-100%; CAR-T later lines 62%, 95%CI 47-82%; p = 0.05). Additionally, 12 (23%) of patients received CAR-T immediately after ASCT (9 after ASCT(2), 3 after ASCT(3)). Baseline demographics in these 12 patients, CAR-T(ASCT), were comparable to the others who had chemoimmunotherapy as the last salvage therapy prior to CAR-T [CAR-T(chemo)], except a smaller proportion received bridging therapy (33% vs. 73%, p = 0.01). The CAR-T (ASCT) group had significantly prolonged PFS (median PFS - not reached [95%CI 3-not reached (NR)] vs. 3 months [95% CI 3-4 months]), and OS (median OS - NR, [95%CI 10.34-NR] vs. 15.1 months, [95%CI 11.9 - NR], p = 0.03). Updated analysis will be presented at the meeting with longer follow up (Figure 1). Conclusion: CAR-T use at the earliest current approved indication may confer survival advantage. Referral for earlier use of CAR-T remains low at only one third of our CAR-T practice volume. CAR-T use for relapse immediately after ASCT appear to have longer PFS and OS than after other systemic salvage therapy, although contributing parameters such as the need for bridging therapy requires further study. While patients who are chemo-refractory to second line chemotherapy may demonstrate chemo sensitivity with third line chemotherapy, PFS is shorter for ASCT(3). Comparison between ASCT(3) and CAR-T (2, chemorefractory) require larger cohorts with longer follow-up. Disclosures Bennani: Affimed: Research Funding; Purdue Pharma: Other: Advisory Board; Kite/Gilead: Research Funding; Verastem: Other: Advisory Board. Ansell:Takeda: Research Funding; ADC Therapeutics: Research Funding; Trillium: Research Funding; Bristol Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; AI Therapeutics: Research Funding. Lin:Juno: Consultancy; Legend BioTech: Consultancy; Merck: Research Funding; Takeda: Research Funding; Gamida Cells: Consultancy; Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vineti: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding.
Infused Autograft-Absolute Lymphocyte Count Predicts Superior Survival in Diffuse Large B-Cell Lymphoma Patients Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation: A Matched-Control Study
Burgstaler, Edwin A. , Porrata, Luis F. , Jacob, Eapen K., Inwards, David J. , Ansell, Stephen M. , Micallef, Ivana N. , Johnston, Patrick B. , Winters, Jeffrey L. , Villasboas, José C. , Paludo, Jonas , Markovic, Svetomir N.

Blood | February 6, 2021 | Volume: 136 | Issue: Supplement 1 | Pages: 8-9

10.1182/blood-2020-133854 Get It

Introduction Day 15 absolute lymphocyte count (ALC-15) recovery after autologous peripheral blood hematopoietic stem cell transplantation (APBHSCT) is recognized as a prognostic factor for survival. ALC-15 recovery is directly dependent on the amount of collected and infused autograft-absolute lymphocyte count (A-ALC). Our group published a double-blind phase III study which showed that patients infused with an A-ALC ≥ 0.5 x 109 cells/kg experienced superior survival post-APBHSCT. Based on the results from our phase III study, on April 1, 2017, our Bone Marrow Transplant Program changed our standard clinical practice to collect an A-ALC ≥ 0.5 x 109 cells/kg in addition to stem cells for lymphoma patients undergoing APBHSCT. To continue to assess the prognostic ability of A-ALC, we evaluated the overall survival (OS) and progression-free survival (PFS) of diffuse large B-cell lymphoma (DLBCL) patients that underwent APBHSCT after April 1, 2017 compared with a matched-control group in a 1:1:1 ratio with DLBCL patients infused with an A-ALC &lt; 0.5 x 109 cells/kg or an A-ALC ≥ 0.5 x 109 cells/kg prior to April 1, 2017. Methods Eight-five consecutive DLBCL patients after our practice changed on April 1, 2017 received an A-ALC ≥ 0.5 x 109 cells/kg. For each DLBCL patient infused with an A-ALC ≥ 0.5 x 109 cells/kg after April 1, 2017, the set of potential controls was restricted to those DLBCL patients infused with an A-ALC &lt; 0.5 x 109 cells/kg and an A-ALC ≥ 0.5 x 109 cells/kg prior to April 1 2017 . Within this group of potential controls, the subjects were chosen who best matched for the cases in terms of clinical risk variables, including gender, age, stage, lactate dehydrogenase (LDH), performance status, extra-nodal disease, International prognostic index (IPI), and disease status prior to APBHSCT (complete or partial response), using the GREEDY algorithm. Cases were defined as DLBCL patients infused with an A-ALC ≥ 0.5 x 109 cells/kg starting from April 1 2017. Control 1 was defined as DLBCL patients infused with an A-ALC &lt; 0.5 x 109 cells/kg prior to April 1 2017. Control 2 was defined as DLBCL patients infused with an A-ALC ≥ 0.5 x 109 cells/kg prior to April 1 2017. We truncated the survival follow-up to 3 years starting from the date of transplant to match follow-up time between cases and controls. Both matched cases and control groups patients received BEAM conditioning. This retrospective study was approved by the Mayo Clinic Institutional Review Board according to the regulation of the Declaration of Helsinki. Results Cases, control 1 and control 2 were balanced to the clinical risk variables; age (p = 0.8); gender (p = 0.9); LDH (p = 0.6); stage (p = 0.3); performance status (p = 0.5); extra-nodal disease (p = 0.2); IPI (p = 0.6); and clinical status prior to transplant (p = 0.2). Figure 1A showed the OS and figure 1B the PFS. Both the cases and control 2 showed superior OS and PFS in comparison to control 1. Cases and control 2 showed overall similar OS and PFS. Multivariate analysis including all patients continue to depict the A-ALC ≥ 0.5 x 109 cells/kg as an independent predictor for OS (HR = 0.382, 95%CI=0.241-0.605, p &lt; 0.0001) and PFS (HR = 0.437, 95%CI = 0.279-0.629, p &lt;0.0001). Subgroup analysis, including all patients, shows superior OS and PFS for patients infused with an A-ALC ≥ 0.5 x 109 cells/kg for each of the following clinical variables: age [&gt; 60 years: OS (p &lt;0.0001); PFS (p &lt;0.0001) or ≤ 60 years: OS (p &lt;0.01); PFS (p , 0.02)]; extra-nodal disease [&gt; 1: OS (p &lt;0.008); PFS (p &lt;0.01) or ≤1: OS (p &lt; 0.001): PFS (p &lt;0.0005)]; IPI [&gt; 2: OS (p &lt;0.01); PFS (p &lt;0.02) or ≤ 2: OS (p &lt;0.0008); PFS (p &lt;0.0006)]; LDH [abnormal: OS (p &lt;0.006); PFS (p &lt;0.005) or normal: OS (p &lt;0.002); PFS (p &lt;0.002)]; performance status [&gt; 1: OS (p &lt;0.04); PFS (p &lt;0.03) or ≤ 1: OS (p &lt;0.0001); PFS (p &lt;0.0001)]; stage [I/II: OS (p &lt;0.006); PFS (p &lt;0.006) or III/IV: OS (p &lt;0.002); PFS (p &lt;0.001)]; response prior to transplant [complete response: OS (p &lt;0.0007); PFS (p &lt;0.0001) or partial response: OS (p &lt;0.01); PFS (p &lt;0.02)]. Conclusion Our match-control study continues to support the results of our Phase III study showing that the infusion of A-ALC is a prognostic factor for survival of DLBCL patients undergoing APBHSCT. Our studies support the practice of not only collecting enough stem cells (i.e., CD34) for hematologic engraftment, but also enough immune effector cells (i.e., A-ALC) to improve clinical outcomes in DLBCL patients post-APBHSCT. Figure 1 Disclosures Ansell: Regeneron: Research Funding; Bristol Myers Squibb: Research Funding; Trillium: Research Funding; ADC Therapeutics: Research Funding; Takeda: Research Funding; AI Therapeutics: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding.