Characteristics and Outcome of Patients with Acute Myeloid Leukemia (AML) Refractory to One Cycle of High Dose Cytarabine-Based Induction Chemotherapy.

Abstract Abstract 1038 Poster Board I-60 Background: Outcome of patients (pts) with AML refractory to initial induction is assumed to be poor but the available data is limited. Furthermore, pts refractory to standard dose cytarabine-based regimens may be salvaged with high dose ara-C (HiDaC, defined as daily ara-C dose ≥ 1 g/m2). Information on the outcome of pts refractory to initial HiDaC - based induction is more limited. Aim To better characterize predictors of poor response to HiDaC-based induction and to evaluate the outcome of pts refractory to such induction regimens. Methods: We identified pts treated with induction regimens containing HiDaC at the University of Texas – M D Anderson Cancer Center who did not achieve a compete remission (CR) after one cycle of induction. We examined their pre-treatment characteristics and compared them with similar pts achieving a CR. We also examined their response to salvage chemotherapy and outcome. Results: Among 1179 pts treated with HiDaC-based induction therapy from 1995 to 2009, 285 were primary refractory to one course of induction. Their median age was 59 (range, 18 - 85). Median pretreatment WBC was 9.0 × 109/L (range, 0.3 – 394 × 109/L). Cytogenetics included-5/-7/complex 101 (35%), diploid 85 (30%), other intermediate 98 (34%), favorable 1 (<1%). 165 (58%) pts had antecedent hematological disorder. Induction regimens used included HiDaC with anthracyclines (n=181, 64%), HiDaC with non-anthracycline chemotherapy (fludarabine, clofarabine, topotecan, and troxacitabine) (n=104, 36%) Pts with primary refractory disease were older (Median age 59 vs. 56; p=000004), more likely to have chromosome 5/7 or complex cytogenetic abnormalities (P=0.0001), more likely to have AHD (p=0.0001), and had a higher presentation WBC (P=0.036), but not a higher incidence of FLT3 mutations (p=0.85) than those achieving CR. Primary refractory disease was not more likely with non-anthracycline containing regimens than those with anthracyclines (p=0.58). Salvage chemotherapy included combination chemotherapy in 111 (39%)(non-ara-C regimen in 40, containing ara-C in 71), single agent chemotherapy in 64 (22%), allogeneic stem cell transplant in 22 (8%) and none in 88 (31%). Forty-three (15%) pts responded to salvage including 35 CR and 8 CRp. 114 (58%) pts were resistant and 35 (18%) died; 5 (3%) were lost to follow-up. With a median follow-up of 115 weeks (range 8 – 347 weeks) in pts responding to salvage, 21 pts (7%) were alive and in CR, for at least 6 months including 14 who underwent an allogeneic stem cell transplant (median overall survival for these 21 pts, 30 months; range, 13 to 87 months). Conclusions: Outcome of pts with disease refractory to HiDaC-based induction is poor. Alternative strategies are needed in these pts who are likely to be resistant to standard chemotherapy. Disclosures: No relevant conflicts of interest to declare.

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Allogeneic Stem Cell Transplant Versus Tandem High-Dose Melphalan for Front-Line Treatment of Deletion 13q14 Myeloma – An Interim Analysis of the German DSMM V Trial.

Blood ◽

10.1182/blood.v114.22.51.51 ◽

2009 ◽

Vol 114 (22) ◽

pp. 51-51 ◽

Cited By ~ 12

Author(s):

Stefan Knop ◽

Peter Liebisch ◽

Holger Hebart ◽

Ernst Holler ◽

Monika Engelhardt ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Interim Analysis ◽

Stem Cell Transplant ◽

High Dose ◽

Cell Transplant ◽

Allogeneic Stem Cell Transplant ◽

High Dose Melphalan

Abstract Abstract 51 Background Allogeneic stem cell transplantation (allo SCT), a treatment modality based on transfer of immunocompetent donor lymphocytes offers curative potential to subjects with a variety of hematological cancers. In multiple myeloma (MM), high-dose melphalan followed by autologous stem cell transplantation (auto SCT) is adopted as a standard of care. However, it remains palliative since virtually all patients (pts) relapse and renders allo SCT an option of interest. Deletion of chromosome 13q14 (13q-) in MM has been shown to negatively impact prognosis. Therefore, improvement of therapy for 13q- pts is highly desirable. Patients and methods A prospective two-arm multi-center trial (DSMM V) was set up by our group to compare tandem high-dose melphalan 200 mg/m2 (HD Mel) with a reduced intensity conditioning allo-SCT after one cycle of HD Mel for 13q- MM. Eligibility criteria were 13q- on bone marrow FISH analysis; age up to 60 years; newly diagnosed MM in Salmon and Durie stages II and III; and measurable disease. Allocation to either treatment arm was by availability of an HLA-matched (one mismatch allowed) volunteer related (VRD) or unrelated donor (VUD). Initially, all pts received four cycles of anthracycline/dexamethasone-based induction followed by chemomobilization of peripheral blood stem cells (PBSCT) and one cycle of HD Mel. Allogeneic SCT was performed after preparation with fludarabine (30 mg/m2 for 3 consecutive days) and melphalan 140 mg/m2. ATG was administered for VUD transplants. Results 199 pts with a median age of 53 (range, 30 – 60) years were enrolled between October 2002 and March 2007 and included in this interim analysis. Sixty-seven percent had stage III disease. Allo SCT was performed in 126 of 199 pts (63%), 76 of whom (60%) received VUD allografts. The remaining 73 subjects uniformely received tandem HD Mel. Pts following allo SCT were more likely to achieve CR (59%) when compared to tandem HD Mel (32%; p=.003) within one year after end of therapy. Similarly, overall response rate was significantly higher with allo SCT (91% versus 86%; p=.003). Of note, depth of response to allo SCT was not associated with presence of acute graft-versus-host disease (GVHD): 62% CR with grades II to IV GVHD vs 58% CR with grades 0 and I (p=.75). Treatment-related mortality (TRM) at 2 years from allo SCT was 16/126 (12.7%). At a median follow up of 25 months for tandem HD Mel and 34 months for allo SCT, projected 3-year overall survival is 72% (auto) and 60% (auto/allo SCT; p=0.22), respectively. Conclusions This is the largest trial on first-line allogeneic stem cell transplant in MM so far. Our interim results show a higher CR rate in FISH 13q- subjects undergoing allo SCT when compared to tandem HD Mel. Despite a majority of allografts in our study being delivered from unrelated donors, TRM was comparable to trials confined to sibling transplants. At a relatively short follow-up, there is not yet a difference between both arms regarding OS, albeit longer follow-up may be important as previously described. This as well as analysis of the impact of donor type and chronic GVHD on outcome will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

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High Dose Cytarabine and Mitoxantrone in Combination with Dasatinib As Active Induction Therapy in Adult Patients with Philadelphia Chromosome Positive (ph+) Acute Lymphoblastic Leukemia (ALL)

Blood ◽

10.1182/blood.v120.21.4293.4293 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4293-4293

Author(s):

Nicole Lamanna ◽

Mark Weiss ◽

Ellin Berman ◽

Mark G. Frattini ◽

Mark Heaney ◽

...

Keyword(s):

Stem Cell ◽

Dose Level ◽

Induction Therapy ◽

Stem Cell Transplant ◽

Philadelphia Chromosome ◽

High Dose ◽

Cell Transplant ◽

Allogeneic Stem Cell Transplant ◽

High Dose Cytarabine

Abstract Abstract 4293 Introduction: The Philadelphia chromosome is the most frequent cytogenetic abnormality in adult ALL, with an overall incidence of 20–30%. When treated with conventional therapy, adult patients with Ph+ ALL have an extremely poor prognosis. While current chemotherapy regimens typically induce complete responses (CRs) in the majority of patients, the quality of remission is poor as most patients relapse within 6–11 months of treatment and subsequently die from the disease. The 1 and 5-year overall survival rates for patients treated with imatinib-based chemotherapy regimens is approximately 60% and 30%, respectively. Previously we in collaboration with others have reported a Phase III randomized study of high-dose cytarabine and mitoxantrone (ALL-2 regimen) as induction therapy versus a more traditional treatment regimen with vincristine-prednisone based induction therapy in newly diagnosed adult ALL patients (Weiss, ASCO 2005). This study was conducted prior to the routine use of tyrosine kinase inhibitors (TKIs) for Ph+ disease. In that randomized study, there were 16 patients with Ph+ ALL treated with the frequency of CRs on the ALL-2 regimen 85% compared to 47% of patients treated on the vincristine-prednisone based arm. At 6 year follow-up, 26% of Ph+ patients treated with the ALL-2 regimen were alive compared to 0% of Ph+ ALL patients treated on the vincristine-prednisone induction arm. Based on this initial favorable response seen with the ALL-2 regimen in Ph+ patients and the emerging use of TKI therapy in Ph+ALL, dasatinib was added to this therapeutic regimen. This is the first report of this combination in newly diagnosed patients with Ph+ ALL or blastic phase CML patients. Methods: Eligible patients included previously untreated or treated adults with a diagnosis of Ph+ ALL or lymphoid blast crisis of known CML. Patients must have evidence of t(9;22) in leukemic cells based on chromosomal or molecular analysis. Patients received induction therapy with high-dose cytarabine (3000 mg/m2 IVPB daily, days 1–5) and mitoxantrone (80mg/m2 IVPB on day 3 for patients ≤ 65 yrs or 40mg/m2 for patients >65 yrs) in combination with dasatinib. Patients in the phase I portion of the study were assigned to one of 3 successive dose cohorts of dasatinib: dose level 1: 70mg daily, dose level 2: 100mg daily; dose level 3: 140mg daily, starting on day 1. Patients then received treatment with Consolidation A: vincristine, dexamethasone, and dasatinib. Following consolidation A, patients who achieved a CR and were ≤ 70 years of age and had a suitable HLA donor were referred for allogeneic stem cell transplant. The remaining patients continued consolidation and maintenance therapy per the ALL-2 regimen with dasatinib as per protocol. Results: Seven patients with Ph+ disease were enrolled between 3/2010-11/2011 (Table 1). All (100%) achieved complete remission after induction; 6 of the seven patients (86%) were in both cytogenetic and molecular remission. Although the numbers are small, there does not seem to be a difference in response depending upon the dose level of dasatinib administered. One patient was taken off study due to recurrent gastrointestinal issues but continued to be followed for response and survival and completed induction therapy as per protocol. Six of the seven patients (86%) went on to receive allogeneic stem cell transplant in first remission. The patient who was ineligible for allogeneic stem cell transplant due to multiple comorbidities continues on maintenance chemotherapy as per protocol. Two patients have died in remission due to post transplant complications. One patient became MRD positive post-transplant and is on nilotinib therapy. Median overall survival has not been reached with median follow-up greater than 20 months. Conclusions: The addition of dasatinib to high-dose cytarabine and mitoxantrone induction therapy for patients with Ph+ ALL is tolerable and efficacious. Patients achieved a higher frequency of CRs compared to our historical study that did not use TKI-based therapy in this patient population. Long-term follow-up of these patients is ongoing. Disclosures: Lamanna: Bristol Meyers Squibb: Research Funding. Off Label Use: dasatinib as part of initial therapy for patients with Philadelphia chromosome + ALL.

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BEAM Versus Single Agent High Dose Melphalan (HDM) Conditioning Regimen for Autologous Hematopoietic Stem Cell Transplant (ASCT): A Retrospective Matched Analysis in Relapse/Refractory Hodgkin Lymphoma

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2018.12.773 ◽

2019 ◽

Vol 25 (3) ◽

pp. S187-S188 ◽

Cited By ~ 1

Author(s):

Panayotis Kaloyannidis ◽

Hani Al Hashmi ◽

Muhammad Shahzad Rauf ◽

Infran Maghfoor ◽

Harbi Salman ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Single Agent ◽

Conditioning Regimen ◽

High Dose ◽

Cell Transplant ◽

Hematopoietic Stem ◽

High Dose Melphalan ◽

Refractory Hodgkin Lymphoma

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Rituximab in Combination with High-Dose Steroids in Advanced, Refractory Chronic Lymphocytic Leukaemia.

Blood ◽

10.1182/blood.v110.11.4719.4719 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4719-4719

Author(s):

John Quinn ◽

Sajir Mohamedbhai ◽

Marilyn Treacey ◽

Shirley D’Sa ◽

Amit Nathwani

Keyword(s):

Stem Cell ◽

Chronic Lymphocytic Leukaemia ◽

Stem Cell Transplant ◽

Lymphocytic Leukaemia ◽

Median Number ◽

High Dose ◽

Cell Transplant ◽

Allogeneic Stem Cell Transplant ◽

Post Transplant ◽

Reduced Intensity

Abstract High-dose methlyprednislone (HDMP) is active in refractory chronic lymphocytic leukaemia (CLL), and rituximab, although showing limited efficacy as a single agent, is effective when used in combination with other cytotoxic agents. Early relapse (<12 months) after purine-analogue based treatment poses a difficult management problem as older patients may be unable to tolerate treatment intensification. This retrospective audit examines the outcome in patients with advanced, refractory/relapsed CLL treated with a combination of high-dose steroids and rituximab. Eleven patients with CLL were treated with rituximab (375mg/m2) and high-dose steroids between 2003 and 2007. Ten patients had advanced and/or refractory disease and one patient had severe autoimmune haemolytic anaemia complicating early-stage CLL. Median age was 70 (range 54–82) and there were 7 male and 4 female patients. Nine patients had Binet stage C disease. Six of the 7 patients for whom results were available had germ-line variable heavy chain immunoglobuliun genes. Median number of prior treatments was 2 (range 1–6) with 9 patients having already received a fludarabine based-regimen. Six patients received a combination of rituximab and high-dose methylprednisolone (1gm/m2 on days 1–5) and 5 patients received a combination of rituximab and high-dose dexamethasone (40mg daily on days 1–4) and. Cycles were repeated every 28 days and the median number of cycles received was 4 (3–6). Antiviral and anti-PCP prophlaxis with aciclovir and co-trimoxazole was routinely prescribed. Response was assessed according to the NCI working group criteria. There was one complete response (CR) and 7 partial responses (PR). Furthermore, 2 of the patients who achieved a PR were successfully salvaged prior to reduced-intensity allogeneic stem-cell transplant and both remain in complete remission (CR) post-transplant. The other 3 patients had minor responses that did not meet NCI response criteria. Median duration of response was 13 months (6–35), excluding the 2 patients who received allogeneic transplants. Three patients required hospital admission with infective complications during treatment. No other significant toxicity was observed. 3 patients have died, none of whom had attained a PR. In conclusion, we found that rituximab in combination with high-dose steroids is a safe and well-tolerated combination in patients with advanced refractory CLL. One patient achieved a CR and we observed a PR in 7/11 patients. Importantly, 2 of these patients were successfully salvaged prior to reduced-intensity conditioning allogeneic stem-cell transplant and both remain in CR at 4 and 12 months respectively post-transplant.

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Phase II Study of Combination of the Hypercvad Regimen with Dasatinib in the Front Line Therapy of Patients with Philadelphia Chromosome (Ph) Positive Acute Lymphoblastic Leukemia (ALL).

Blood ◽

10.1182/blood.v114.22.837.837 ◽

2009 ◽

Vol 114 (22) ◽

pp. 837-837 ◽

Cited By ~ 1

Author(s):

Farhad Ravandi ◽

Hagop M. Kantarjian ◽

Deborah A. Thomas ◽

Stefan Faderl ◽

Dan Jones ◽

...

Keyword(s):

Stem Cell ◽

Phase Ii ◽

Research Funding ◽

Stem Cell Transplant ◽

High Dose ◽

Cell Transplant ◽

Newly Diagnosed ◽

Allogeneic Stem Cell Transplant ◽

Median Response ◽

Platelet Recovery

Abstract Abstract 837 Background: Combination therapy with cytotoxic chemotherapy and tyrosine kinase inhibitors has improved the outcome for patients with Ph+ ALL with durable remissions in some patients even without an allogeneic stem cell transplant. The dual Src and Abl inhibitor dasatinib has ∼325 times more potent in vitro kinase inhibition than imatinib against BCR-ABL with significant clinical activity in patients with imatinib-resistant lymphoid blast phase CML (CML-LB) and Ph+ ALL. Aim: To determine the efficacy and safety of combining chemotherapy with dasatinib for treating patients with Ph+ ALL. Methods: In this phase II trial, patients with newly diagnosed Ph+ ALL receive dasatinib 50 mg po bid (or 100 mg daily) for the first 14 days of each of 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate. Patients in CR continue to receive maintenance dasatinib 50 mg po bid (or 100 mg daily) and vincristine and prednisone monthly for 2 years followed by dasatinib indefinitely. Results: We have enrolled in the study 34 patients with untreated Ph+ ALL and 7 patients with 1 prior cycle of chemotherapy (before Ph+/BCR-ABL+ status was known). Patients younger than 50 years old have received a median of 6 cycles (range 2-8) and patients 50 years and older have received a median of 6 cycles (range 1-8). 20 patients are receiving maintenance in CR and two have completed the entire treatment regimen. Median age is 51 years (range 21 – 79); 22 patients were older than 50 years, Median WBC at diagnosis was 13.6 × 109/L (range, 1-276 × 109/L). 12 patients had CNS involvement at presentation. All patients are evaluable for assessment of response to induction; 39 (95%) achieved CR after first cycle or were CR at start. Two patients died before response assessment from infections. Thirty-one of 39 (79%) evaluable patients achieved cytogenetic (CG) CR after 1 cycle; 4 had a major CG response (3 had 5% and one had 15% Ph+), 2 had insufficient metaphases, and 2 are unknown (no CG exam on day 21 marrow). To date, 22 patients (56%) have achieved complete molecular remission (CMR) and another 8 (21%) have achieved a major (but not complete) molecular response (MMR) at a median of 14 weeks from initiation of treatment (range 2 – 59 weeks). Minimal residual disease assessment by flow cytometry is negative in 35 (90%) patients at a median of 3 weeks (range, 2-18 weeks). The median time to neutrophil and platelet recovery for cycle 1 is 18 and 23 days and for subsequent cycles is 15 and 20 days. Grade 3 and 4 adverse events have included bleeding (GI, GU, soft tissue and subdural hematomas)(18), pleural effusions (9), pericardial effusion (1), reversible rise in creatinine (10), deep vein thromboses (6), pulmonary emboli (3), as well as diarrhea, infections, hypophosphatemia, hypokalemia, hypocalcemia, hyperglycemia, and elevated transaminases. With a median follow up of 13 months (range 1-33), 29 patients (71%) are alive and 27 (66%) are in CR; 4 patients died in CR; 1 from an unrelated cardiac event and 3 from infections. Three patients have undergone an allogeneic stem cell transplant. The median disease free survival is 48+ weeks (range,1 to 140+) and the median overall survival is 52+ weeks (range, 3 to 143+). Eight patients have relapsed with a median response duration of 51 weeks (range 23-73) and 6 of them have died. In 5 patients morphological relapse was preceded by flow and molecular relapse. Five relapsed patients had ABL mutations (3 T315I, 1 F359V, and 1 V299L). Conclusion: Combination of chemotherapy with dasatinib is effective in achieving long term remissions in patients with newly diagnosed Ph+ ALL. Disclosures: Ravandi: Bristol Myers Squibb: Honoraria, Research Funding. Kantarjian:Bristol Myers Squibb: Research Funding. Wierda:Genzyme: Research Funding; Genentech: Consultancy, Honoraria. Cortes:Bristol Myers Squibb: Research Funding. O'Brien:Bristol Myers Squibb: Research Funding.

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Outcomes and Treatments of Relapsed AL Amyloidosis Following Stem Cell Transplant

Blood ◽

10.1182/blood.v120.21.1858.1858 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1858-1858 ◽

Cited By ~ 1

Author(s):

Rahma Warsame ◽

Soo-Mee Bang ◽

Shaji K. Kumar ◽

Martha Q Lacy ◽

Francis K Buadi ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Plasma Cells ◽

Conflicts Of Interest ◽

Treatment Options ◽

Autologous Stem Cell Transplant ◽

Al Amyloidosis ◽

Cell Transplant ◽

Post Transplant

Abstract Abstract 1858 Systemic light chain amyloidosis (AL amyloidosis) is a condition where clonal plasma cells produce misfolded insoluble immunoglobulin light chains that deposit in various organs causing progressive organ dysfunction. Chemotherapy and autologous stem cell transplant (ASCT) when eligible is the standard treatment options for patients with AL amyloidosis. There are several studies who report long term outcomes of patient post ASCT. However, there is a paucity of literature describing the outcomes of patients who have received ASCT but have relapsed. We performed a retrospective study to assess the outcomes and treatment regimens employed following relapse after ASCT. Between 1996 and 2009, 410 patients received ASCT at the Mayo Clinic as first line therapy. Of those 410 patients 42 patients died within 3 months of transplant, 64 patients died without documented relapse, 158 patients were alive without documented progression, and 146 patients had documented progression. Those 146 patients are the subject of our study. The median time to hematologic relapse was 2 years (range: 0.2–15.5 years). At relapse, 59 patients were treated with IMiD based therapy, 36 with alkylator based therapy, 24 with bortezomib, 15 with steroids, and 5 with second ASCT. The respective hematologic response rates were 58%, 33%, 50%, 53%, and 60%. The remaining six patients were not evaluable for response for one other following reasons: organ transplants; no further therapy; inevaluable disease. With a median post relapse follow up of 3.6 years, the median overall survival (OS) from the first post ASCT relapse was 4.6 years. The median post transplant follow up was 6.1 years, the median OS for these patients was 7.3 years from the time of transplant. These data provide novel information about outcomes after SCT relapse, which should be useful not only for patients and doctors but also for investigators designing studies for salvage therapies post-transplant. Disclosures: No relevant conflicts of interest to declare.

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The Chemotherapy Regimen IVAC Is Highly Active for Multiply Relapsed and Refractory Hodgkin Lymphoma

Blood ◽

10.1182/blood.v120.21.4863.4863 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4863-4863

Author(s):

Catherine S. Diefenbach ◽

David Kaminetzky ◽

Shannon Andersen ◽

Jane Chin ◽

Barbara MacGregor-Cortelli ◽

...

Keyword(s):

Stem Cell ◽

Hodgkin Lymphoma ◽

Stem Cell Transplant ◽

Chemotherapy Regimen ◽

Conflicts Of Interest ◽

Combined Modality Therapy ◽

Cell Transplant ◽

Refractory Disease ◽

Highly Active ◽

Grade 3

Abstract Abstract 4863 Background: Hodgkin Lymphoma (HL) has a cure rate of 70% with chemotherapy or combined modality therapy. Despite this success, approximately 5–10% of patients have primary refractory disease, and 20–30% of patients will relapse after initial complete remission (CR). Second-line chemotherapy and autologous stem cell transplant (ASCT) approaches are curative for only 50% of patients with relapsed/refractory disease. Maximal cytoreduction prior to ASCT confers the greatest potential benefit, yet the current standard salvage chemotherapy regimens have a low CR rate despite a high overall response rate (ORR), and survival is poor for patients who relapse after ASCT. Allogeneic stem cell transplantation can induce durable remissions in some patients with relapsed and primary refractory HL; however the use of this modality is limited in part by the challenges of achieving adequate disease control prior to transplantation. Novel treatment platforms to maximally debulk these patients and allow them to proceed to successful transplantation are needed. Our group has treated multiply relapsed HL patients with the chemotherapy regimen of Ifosfamide, Etoposide, and Cytarabine (IVAC) and we report a retrospective chart review detailing our experience. Methods: Between January of 2011 and June of 2012, 4 patients with relapsed or primary refractory HL were treated with the chemotherapy regimen IVAC consisting of: Ifosfamide 1,500mg/m2 days 1–5; MESNA 1,500mg/m2 days 1–5, Etoposide 600mg/m2 days 1–5, and Cytarabine 2,000mg/m2 q 12hrs × 4 doses days 1–2 given every 21 days. All patients received growth factor support beginning 24hrs after completion of chemotherapy. All patients received prophylactic antifungal, antiviral, and PCP prophylaxis. Restaging PET/CT was performed after 2 cycles of therapy. All patients received 2 cycles of therapy prior to assessment for transplant. Results: Four patients have been treated to date on this regimen. The mean age of the 4 patients was 35.5 (range 32–43). All patients were male. All patients were heavily pre-treated with a mean of 8 prior chemotherapy regimens (range 7–9) including ICE (Ifosfamide, Carboplatin, Etoposide) and Brentuximab vedotin. Three of the 4 patients had prior stem cell transplant: autologous (n=2), allogneic with subsequent DLI (n=1). All patients tolerated the chemotherapy well. The most common significant adverse events were: grade 3 pneumonia (1/4 patient), grade 3 febrile neutropenia (1/4 patients), grade 3 neutropenia (4/4 patients), grade 3 anemia (4/4 patients), grade 3 thrombocytopenia (4/4 patients). All patients recovered to baseline before initiating cycle 2, and after the completion of therapy. Response was evaluated after 2 cycles of therapy in all patients. Three of 4 patients (75%) had a response giving an ORR rate of 75%. Two of the 3 responding patients had a CR giving a CR rate of 50%, 1 patient had a PR. Response duration was: 6 weeks (n=1), 3 months (n=1), 6 months (n=1). Conclusion: IVAC is highly active, even in heavily pre-treated HL patients, with an ORR of 75% and a CR rate of 50%. With close clinical monitoring hematologic and infectious toxicities were manageable in all patients. The regimen of IVAC may allow disease debulking for multiply relapsed HL patients prior to stem cell transplant. Prospective evaluation of this therapy is ongoing. Disclosures: No relevant conflicts of interest to declare.

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Alternative Consolidation Strategy after High Dose Methotrexate, Rituximab and Temozolamide in Primary CNS Lymphoma - the Henry Ford Experience

Blood ◽

10.1182/blood-2020-142058 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 5-5

Author(s):

Joyce Philip ◽

Shivani Sharma ◽

Vijayalakshmi Donthireddy

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Primary Cns Lymphoma ◽

Autologous Stem Cell Transplant ◽

Cns Lymphoma ◽

High Dose ◽

Cell Transplant ◽

High Dose Methotrexate ◽

Dose Methotrexate

Background: Treatment for primary CNS lymphoma involves a methotrexate-based induction therapy followed by consolidation. The optimal consolidation treatment after induction with a high dose Methotrexate (HD-MTX), Rituximab and Temozolomide regimen has not been fully established. The CALGB 50202 regimen using Etoposide and Cytarabine consolidation was associated with significant toxicity. We sought to review the results of alternative consolidation regimens and evaluate the progression free survival and overall survival. Methods: A retrospective cohort study was conducted to evaluate the efficacy of alternative consolidation regimens such as autologous stem cell transplant and HDMTx alone. Patients diagnosed with primary CNS lymphoma between November 2012 and March 2019 were identified. All patients received the same induction chemotherapy based on the CALGB 50202 protocol. Data was collected for baseline characteristics, progression free survival and overall survival. Results: 38 patients had a diagnosis of primary CNS lymphoma. 15 patients received treatment as per the CALBG 50202 induction protocol with high dose Methotrexate, Rituximab and Temozolomide. Of the 15 patients, 11 patients (69%) achieved a complete remission (CR) after induction therapy. 7 patients received an autologous stem cell transplant for consolidation, 5 patients received HD-MTX alone for consolidation and one patient was placed on Lenalidomide maintenance. 2 patients did not receive any consolidation therapy due to progressive disease and/or death. At a median follow up of 2.7 years for the entire cohort, median PFS was 31.7+ months and median OS was 32.5+ months. At a median follow up of 2.7 years for patients who were consolidated with an autologous stem cell transplant, median PFS and median OS was 27.2+ and 32.5+ months respectively. At a median follow up of 5.5 years for patients who were consolidated with treatments other than transplant, median PFS and OS was 65.6+ months. There were no deaths attributed to treatment related toxicity. To date, 4 patients of the entire cohort have died, with a median survival time among surviving patients of 3.6 years (range, 0.68-7.05 years). There were no deaths attributed to treatment related toxicity. Conclusion: Patients with primary CNS lymphoma who received induction therapy as per CALGB 50202 regimen and received alternative consolidation therapies with either autologous stem cell transplant or HD-MTX based consolidation achieved prolonged PFS and OS comparable if not superior to the Etoposide and Cytarabine consolidation. Results of the ongoing CALGB 51101 trial will determine the utility of EA consolidation. Disclosures No relevant conflicts of interest to declare.

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