Auto Stem Cell Transplantation Research Articles

Retrospective Study Assessing Outcomes of AYA Patients with Lymphoma Following Auto Stem Cell Transplant

Retrospective Study Assessing Outcomes of AYA Patients with Lymphoma Following Auto Stem Cell Transplant

Prognostic Significance of CD30 Expression and Response to Brentuximab Vedotin in Patients with Angioimmunoblastic T Cell Lymphoma

Background Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell lymphoma (PTCL) characterized by a follicular helper T-cell phenotype. The standard frontline treatment for AITL typically involves CHOP or CHOP-like regimens, with consideration for autologous stem cell transplant. A promising treatment option for CD30-positive (CD30+) PTCLs, including AITL, is the anti-CD30 antibody drug conjugate, brentuximab vedotin (BV). The ECHELON-2 study demonstrated equivocal outcomes in CD30+ PTCL patients (pts) who received BV-CHP instead of CHOP. However, response of BV in CD30+ AITL pts is still uncertain. This study aims to evaluate the relationship between CD30 expression and the clinical response to BV in pts diagnosed with AITL. Methods This retrospective IRB approved study conducted at MD Anderson Cancer Center, where we analyzed pts with AITL diagnosed between 1997- 2023. Patient demographics, laboratory data at diagnosis, pathology review, treatment, and treatment response were collected and analyzed. Expression of CD30 expression in neoplastic cells was evaluated by immunohistochemistry and scored in 5% increments. Kaplan- Meier method was used to assess overall survival (OS) and log-rank used to compare different groups. Results This study included a cohort of 339 pts with AITL. Among them, 55 (23%, n=237) had no detectable CD30 expression (CD30=0%),182 (77%, n=237) patients had detectable CD30 expression (CD30>1%), and 102 pts had unknown CD30 expression. Table 1 shows patient characteristics by CD30 expression and response to first-, second-, and third- line BV treatment. There were 113 (48%, n=237) females and 124 (52%, n=237) males with a median age of 66 years. Most patients were Whites (88%, n=196) followed by Black (4%, n=196), and Asian (5%, n=196). Fifty-two (n=122) of pts who were CD30+ had stage III, 43% (n=122) had stage IV (p-value= <0.001), and 38% had BM involvement (p- value= 0.3). For pts with disease showing no CD30 expression (CD30neg) 16% (n=43) of pts had stage III, 70% (n=43) had stage IV, and 48% (n=42) had BM involvement. Auto-Stem cell transplant (ASCT) was performed in 48% of those with CD30+ and 43% of CD30neg. The most common first-line treatment was chemotherapy combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) followed by other CHOP like regimens. In total, 35 pts received BV treatment as first-line, 32 patients received BV in combination with chemotherapy and 3 received BV only. For second-line treatment, 11 received BV treatment and for third- line only 6 received BV. First- line treatment with BV showed better clinical response rates, with 82% achieving complete response (CR, n= 34), followed by second line CR with 56% (n= 9) and third- line with 0% (n= 6). The median OS were similar between those with CD30+ who did or did not receive first line BV (20 months vs. 19 months, p>0.05). The median OS for CD30neg pts who did not receive BV was 25 months (p=0.42). Furthermore, there was no statistically significant difference in OS between pts who underwent a ASCT (CD30+ 24.5 months and CD30neg 32.5 months, respectively) and those who did not (CD30+ 18.5 months and CD30neg 24.5 months, respectively, p- value = 0.29). Conclusion While this study did not find CD30 expression to be a predictor of response to BV treatment or ASCT in AITL pts, it provides valuable insights into the prevalence of CD30 expression and BV response as first- line treatment. Notably, 77% of pts had CD30 expression and pts who received BV as first- line had a higher proportion of CRs compared to pts who received BV as second- and third- line treatments. Further investigations with larger patient cohorts are necessary to determine the prognostic and predictive role of CD30 in AITL. Additional studies analyzing CD30 expression levels in malignant cells, immunoblasts, and macrophages are planned for presentation at the upcoming annual meeting.

Significance of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio and Monocyte-to-Lymphocyte Ratio in the Prognosis of Newly Diagnosed Multiple Myeloma Patients

Background Multiple myeloma is a cancer of the plasma cells, characterized by abnormal proliferation in the bone marrow. In 2023 about 12,590 deaths are expected to occur secondary to the disease. It is important to identify the predictors of disease progression for prognostication.Tumor microenvironment influences the growth of malignant plasma cells. Neutrophilia can enhance tumor growth, angiogenesis and provide a favorable matrix for metastasis. Lymphopenia is also suggestive of disease progression. Hence, an increased neutrophil-to-lymphocyte ratio (NLR) has been linked with a poor prognosis in many cancers. Monocytes are thought to be recruited by tumor cells for suppressing the immune cells and aiding in prolonged survival. In patients with multiple myeloma, a low platelet count is linked to a worse prognosis since a greater marrow myeloma burden leads to inhibition of thrombopoiesis.Hence, a low platelet-to-lymphocyte ratio (PLR) and high monocyte-to-lymphocyte ratio (MLR) are linked with worse prognosis.The aim of our study was to investigate the role of NLR, PLR and MLR in the prognosis of our patients. Methods This is a retrospective study that analyzed patients diagnosed with Multiple Myeloma from 2012 to 2022 at Saint Vincent Cancer Center, Worcester, Massachusetts. We performed a chart review and collected demographics including age at the time of diagnosis, gender, BMI, race. Additionally, we also collected data such as multiple myeloma type, R-ISS staging, complete blood count (cbc), chemotherapy used, auto stem cell transplant, 5-year survival. NLR, PLR and MLR were calculated based on pre-treatment cbc. Based on literature review, cutoffs for High NLR (≥2), Low NLR (<2), High PLR (≥120.00), low PLR (<120.00) and high MLR (≥0.27), and low MLR (<0.27) were made. SPSS was used for analysis of the data. A logistic regression was used to calculate the Odd's ratio (OR). A p value less than equal to 0.05 was considered significant. Results The total number of patients analyzed were 97. 47.4% (n=46) were females and 52.6% (n=51) were males. Mean age at diagnosis was 69.3 years. Mean BMI was 30.16 kg/m 2. 35.1% (n=34) of the patients had IgG subtype. 36.1% (n=35) of our study population belonged to R-ISS stage 2. 38.1% (n=37) of the patients were treated with lenalidomide, bortezomib, dexamethasone combination. Mean NLR was 3.4, mean PLR was 166.949 and mean MLR was 0.46. 66% (n=64) of the patients belonged to the high NLR group, 61.9% (n=60) to the high PLR group and 64.9% (n=63) to the high MLR group. Out of 97 patients, 56.7% (n=55) were alive at 5 years. High NLR (≥2) was associated with lower odds of 5-year survival with a p value of 0.037 and a 95% confidence interval (0.095-0.931). High MLR (≥0.27) was associated with lower odds of 5-year survival with a p value of 0.042 and a 95% confidence interval (0.124-0.962). PLR did not correlate with 5-year survival and was not statistically significant (p value of 0.157). Conclusions Based on our study, a high NLR (≥2) and high MLR (≥0.27) were associated with lower odds of 5-year survival. Hence NLR and MLR are independent prognostic factors in newly diagnosed multiple myeloma patients which can be economical and effective methods for early evaluation of patient prognosis.

Busulfan/Cyclophosphamide Compared with Melphalan as a Conditioning Regimen for Autologous Transplantation of Multiple Myeloma: A Long-Term Assessment.

Melphalan was poorly available in mainland China. The aim of this study is to explore the dose-adjusted busulfan/cyclophosphamide (BU/CY) as an alternative regimen in auto stem cell transplantation (ASCT) for multiple myeloma (MM). A total of 105 newly diagnosed MM patients undergoing ASCT during May 2012 and August 2017 were retrospectively analyzed. The BU/CY regimen was applied to 64 patients. Busulfan (9.6 mg/kg or 8.0 mg/kg in total) and cyclophosphamide (3.6 g/m2 or 3.0 g/m2 in total) were administered according to the creatinine clearance rate (CCR). A high-dose melphalan (HDMEL) regimen (200 mg/m2) was given to the other 41 patients. At a median follow-up of 65 (1~119) months, estimated overall survival (OS) and progression-free survival (PFS) at 104 months in the BU/CY and HDMEL groups were 35.6% vs. 20.5% (p = 0.263) and 20.2% vs. 2.4% (p = 0.035), respectively. The median overall survival (OS) and PFS of the HDMEL and BU/CY groups were 55 vs. 70.5 months and 26 vs. 46.5 months, respectively. In multivariate analysis, the BU/CY regimen was found to be the only protective factor for PFS. No lethal toxicity was found in the BU/CY group, and treatment-related mortality (TRM) in 100 days was similar to the HDMEL group. MM patients may also benefit from the dose-adjusted BU/CY regimen.

Prediction of success of CD34+ collection for autotransplantation in children

Intensive chemotherapy with autologous stem cell transplantation is a therapeutic tool used in paediatric oncology. In adult patients, a peripheral blood CD34+ cell count superior to 20/μL enables an adequate collection of peripheral blood stem cells. There are no recommendations for children. This study aimed to determine whether the count of circulating CD34+ cells on the day before cytapheresis predicts successful collection in paediatric patients. We retrospectively studied all paediatric patients who underwent apheresis for stem cell autotransplantation in the CHU of Rennes between 2010 and 2019. Successful apheresis was defined as a collection superior to 3×106 CD34+/kg. "Success" and "failure" groups were compared. In total, 122 apheresis procedures were performed in 105 patients. It was a successful procedure in 81% of patients and a failure in 19% of patients. A minimal cut-off of circulating CD34+ count superior to 13/μL on D-1 allowed us to predict a collection of at least 3×106 CD34+/kg (PPV 94,8%, NPV 51,4%). For children aged<6 years, the association with leucocyte increase during the 5 days before the procedure improved the prediction of success. The peripheral blood CD34+ cell count is a predictive factor for successful collection in paediatric patients. The minimal cut-off that allows an adequate collection of peripheral blood stem cells is inferior to the minimal cut-off in adult patients. Nevertheless, this minimal number of circulating CD34+ cells is insufficient to predict the success or failure of apheresis in patients younger than 6 years of age.

Efficacy and Safety of Retreatment with Brentuximab Vedotin in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma or CD30-Expressing Peripheral T Cell Lymphoma

Introduction Brentuximab vedotin (BV) is approved for the treatment of adult patients (pts) with classical Hodgkin lymphoma (cHL), systemic anaplastic large cell lymphomas (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL). BV has been evaluated in combination with doxorubicin, vinblastine, and dacarbazine (A+AVD) in adult pts with advanced stage cHL in ECHELON-1 (Ansell S, 2022) and in combination with cyclophosphamide, doxorubicin, and prednisone (A+CHP) in pts with sALCL, PTCL-not otherwise specified (NOS), and angioimmunoblastic T-cell lymphoma (AITL) in ECHELON-2 (Horwitz S, 2022), demonstrating BV is well tolerated with a favorable efficacy profile in the first-line setting. Moreover, BV is approved as monotherapy for treatment of adults with cHL at high risk of relapse as consolidation therapy post autologous stem cell transplant, as well as in relapsed or refractory (r/r) sALCL. BV has also been studied in r/r cHL after auto-stem cell transplant (Younes A, 2012) and retreatment setting (Trümper L, 2020), with favorable efficacy. CD30 expression persists after BV treatment and SGN35-006 demonstrated that BV monotherapy is an effective retreatment option in pts with r/r cHL or sALCL who previously achieved an objective response with BV monotherapy (Bartlett N, 2014). Herein, we present efficacy and safety results from a phase 2 study, where BV was evaluated in pts with r/r cHL or CD30-expressing PTCL who previously received BV either alone or in combination. Methods SGN35-028 (NCT03947255) is a multicentered, single arm, phase 2 clinical trial that enrolled adult pts with r/r cHL and sALCL or other CD30-expressing PTCL who were previously treated with a BV-containing regimen at least 6 months prior that had evidence of an objective response, and subsequently experienced disease progression or relapse after discontinuing treatment. Pts were treated with BV 1.2 or 1.8 mg/kg intravenously every 3 weeks until disease progression or unacceptable toxicity. The primary endpoints were objective response rate (ORR) and the safety and tolerability of BV retreatment. Results Of the 12 pts enrolled, 11 received at least 1 dose of study treatment including 5 pts with cHL and 6 pts with PTCL (4 pts with sALCL, 1 pt with PTCL-NOS, 1 pt with AITL). Both pts with non-ALCL PTCL had CD30 expression on 1% of tumor cells. Of the 11 pts that received at least 1 dose of study treatment, most were Black or African American (55%), not of Hispanic, Latino, or Spanish origin (91%), and <65 years old (73%). Pts received a median of 8 doses of BV (range: 1, 16) over a median of 25 weeks (range: 3, 55), 3 pts (27%) had dose reductions. Three pts were still on treatment as of data cutoff date. For pts with cHL, median time from initial diagnosis to first dose was 76.2 months (range: 34, 162), 2 pts achieved complete response (CR) and 3 pts partial response (PR) on prior BV therapy, median time from completion of last BV therapy to first dose was 28.2 months, and median age was 31 years (range: 28, 55). The ORR per investigator assessment was 60% (95% CI: 14.7, 94.7) with 1 pt achieving CR. For pts with PTCL, median time from initial diagnosis to first dose was 31.2 months (range: 23, 138), 5 pts achieved CR and 1 pt PR on prior BV therapy, median time from completion of last BV therapy to first dose was 20.1 months, and median age was 63 years (range: 35, 77). The ORR per investigator assessment was 83% (95% CI: 35.9, 99.6) with 4 pts achieving CR. The 4 pts with sALCL had an ORR of 100% with a CR rate of 75%. Eight pts discontinued study treatment, 4 pts discontinued treatment due to disease progression, 2 pts due to investigator decision, and 2 pts due to treatment emergent adverse events (TEAEs), both with peripheral sensory neuropathy. Thirty-six percent of pts experienced ≥ Grade 3 treatment-related TEAEs, 2 (18%) each for neutropenia and peripheral sensory neuropathy and 1 (9%) each for amylase increased, fatigue, malaise, and nausea. One pt experienced a Grade 5 adverse event of decreased appetite related to progressive PTCL disease that was not treatment related. Conclusions Preliminary results from this study show BV is a viable retreatment option for adults with r/r cHL, sALCL, and PTCL. Moreover, safety results were consistent with the known safety profile and no new safety signals were observed. This study is ongoing, updated efficacy and safety results will be presented at the meeting.

Experience of successful autologous hematopoietic stem cell transplantation in patients with an unfavorable prognosis of systemic scleroderma

One of the methods of treating severe forms of systemic scleroderma is hematopoietic stem-cell autotransplantation (auto-HSCT). The article describes two clinical cases of auto-HSCT followed by rituximab (RTM) therapy in patients with diffuse systemic scleroderma with progressive interstitial lung disease (ILD), high immunological activity, high skin score, and an unfavorable prognosis. The assessment of the course of these diseases was carried out in the course of dynamic observation of patients for 10–11 years. In all cases, auto-HSCT followed by RTM made it possible to achieve remission / low activity, as well as to stabilize the progressive of ILD.

IgD-Lambda Multiple Myeloma without Renal Failure: An Unusual Presentation

Immunoglobulin D (IgD) multiple myeloma is a rare form of myeloma having often an aggressive course, affecting 2% of all cases. It shows frequentely renal failure, Bence Jones proteinuria and the difficulties of diagnosis. We report a case of a 59 years old man with IgD multiple myeloma associated with good renal function. The patient was hospitalized in the hematology department for bone pain and alteration of the general condition. A further evaluation for multiple myeloma revealed presence of a monoclonal protein band in Beta2 region in serum protein electrophoresis (SPE). Urine protein electrophoresis (UPE) showed presence of BenceJones proteinuria.The immunofixation electrophoresis (IE) of the serum reported as IgD-Lambda paraproteinaemia. Laboratory studies showed also an anemia , hypercalcemia, but fortunatuly, our patient did not have renal failure, as is common with myeloma. Bone marrow examination showed infiltration by plasma cells. Thus, the patient was put on chemotherapy and stem cell autotransplantation with a good clinical and biological improvement. This case is reported to emphasize the importance of performing IgD immunofixation routinely for all suspected multiple myeloma patients because many cases are erroneously diagnosed as light chain disease. And it describes a rare case of an even rarer and uncommon situation and highlights the fortunate situation of this patient's unfortunate disease.

Impact of a shared-care model between community and academic centers for facilitating access to allogeneic and autologous stem cell transplantation.

1510 Background: Despite curative or disease-controlling roles in AML/MDS and MM, access to allogeneic (allo) and autologous (auto) hematopoietic stem cell transplantation (SCT) remains far from universal. Socioeconomic status (SES) and geographic distance from SCT centers have been shown to be barriers to SCT access. In 2016, Hartford HealthCare (HHC) and the Memorial Sloan Kettering Cancer Center (MSK) pioneered a Shared-Care Model (SCM) to streamline access to allo and auto SCT at MSK, featuring a dedicated nurse SCT coordinator, shared hematology tumor boards, MSK-led didactics for HHC providers, and an electronic health record sharing pipeline. We sought to determine if this has improved access to SCT for HHC patients. Methods: A retrospective chart review was conducted of HHC patients aged 18-70 with new diagnoses of AML, MDS, and MM between 2016 and 2020. Socioeconomic status (SES) was estimated by 9-digit zip-code using the Area Deprivation Index (ADI), shown to be a surrogate for healthcare access. Referral or not to a SCT center, referral to MSK through the SCM, and reasons for non-referral were abstracted from the medical record. For patients referred for SCT at MSK, we also captured the number of peri-SCT days in New York City (NYC) and number of subsequent MSK and HHC clinic visits/hospitalizations within 1-year post-SCT. Results: A total of 126 patients was included, with 81 (64%) treated for AML/MDS and 45 (36%) for MM. The median age was 60 years (interquartile range [IQR]: 53-66). The majority were white (n = 101, 80%) followed by 10% (n = 13) Black/African American; 10% (n = 12) were of Hispanic ethnicity. The median ADI percentile was 38 (IQR: 20-51; higher percentiles reflect decreased SES). The median ADI for MSK SCT referrals from New York, New Jersey, and Connecticut 2016-2020 for the same indications was 19 (IQR: 10-30, p &lt; 0.001). A total of 90 patients (71%) were referred to SCT centers. Leading reasons for no referral were favorable-risk disease (n = 10), goals of care (n = 9), and death prior to referral (n = 5); 3 patients were not referred due to comorbidities/performance status. No differences were found between patients referred to MSK vs. other centers. Thirty-four HHC patients were referred to MSK (21 AML/MDS, 13 MM), vs. 3 between 2010 and 2015. Twelve patients underwent allo SCT, with median 97 days in NYC (range: 68-247); 8 underwent auto SCT, with median 21 days in NYC (range: 15-48). Conclusions: Our findings show the feasibility of a shared-care model between a non-SCT-providing large regional hospital system and a major academic transplantation center. Close collaboration between institutions may minimize time patients spend away from home. The SES of HHC referrals was lower than the general MSK population, suggesting that a shared-care model may facilitate access to SCT for patients with previous barriers for this potentially curative therapy.

Key markers for diagnosis of minimal residual disease in multiple myeloma

Introduction. Therapeutic advances in recent years, the appearance on the market each time of new drugs that allow patients to achieve complete remission, a long period without progression dictate the need to control treatment by monitoring residual disease in multiple myeloma. Monitoring of multiple myeloma is the detection of a small number of tumor cells after therapy in a patient, which may be the cause of recurrence of the disease – control of minimal residual disease (MRD). This article discusses the key diagnostic markers (CD45, CD56 and CD19) of minimal residual multiple myeloma disease at initial diagnosis and after induction therapy. There are various diagnostic methods of research that can reliably assess the response to therapy and predict the occurrence of relapse. The main methods for detecting MRD are allele-specific polymerase chain reaction, next-generation sequencing and multicolor flow cytometry. The diagnosis of MRD by flow cytometry is the most widely used quite fast, quantitative, sensitive and affordable method, it is used for the primary diagnosis of multiple myeloma, as well as for monitoring MRD. It is important to identify the aberrant immunophenotype during the initial diagnosis for the correct subsequent assessment of MRD. MRD of multiple myeloma is considered an important component in the course of patient therapy before hematopoietic stem cell autotransplantation to assess the effectiveness of therapy, control and prognosis of the disease.The aim of the work MRD-study with the key diagnostic markers in multiple myeloma (CD45, CD56 and CD19).Materials and methods. The study was carried out in 59 patients with multiple myeloma. For all patients, in addition to standard methods of diagnosis and staging of the disease, bone marrow morphology (myelogram) and immunophenotype were examined. Eight-color flow cytometry with a panel of monoclonal antibodies for the diagnosis of plasma cell tumors Euro-Flow 2012 was used to diagnose MRD.Results. MRD was assessed by markers CD45, CD56 and CD19 in patients with multiple myeloma after induction therapy. The incidence of MRD-positivity for CD45 was 87.5 %, for CD56 – 97.5 %, for CD19 – 95.5 %. The incidence of MRD-negative status was for CD45 was 12.5 %, for CD56 – 2.5 % and for CD19 – 4,5 %.Conclusion. The use of a complex of these markers allows the most accurate determination of the MRD-negative status, taking into account the primary immunophenotype of malignant plasma cells.

RD Vs. VRD: What Is the First-Line, Real-Life Management of Multiple Myeloma Patients Ineligible for Stem Cell Auto Transplantation in the Emmy Cohort?

RD Vs. VRD: What Is the First-Line, Real-Life Management of Multiple Myeloma Patients Ineligible for Stem Cell Auto Transplantation in the Emmy Cohort?

Long-Term Survival With Cybord Induction Therapy In Newly Diagnosed Multiple Myeloma

IntroductionWe piloted an induction regimen of cyclophosphamide, bortezomib and dexamethasone (CyBorD)(CBD) in 2006 and showed rapid and deep responses after 4 cycles in patients with newly diagnosed multiple myeloma (MM).1 We subsequently reported equal responses and less toxicity with weekly bortezomib dosing.2 Triplet therapy has since become common in both standard and high risk patients and no other triplet combination has shown results superior to CyBorD.3 We report long-term f/u data for all 63 patients treated on both cohorts at MCA and PMH. MethodsSixty-three patients with newly diagnosed and symptomatic myeloma were enrolled between 2006 and 2008 on a phase II trial of weekly oral cyclophosphamide 300mg/m2, IV bortezomib 1.3 mg/m2 d1, 4, 8, 11 (Cohort1) or 1.5mg/m2 d1, 8, 15, 22 (Cohort2) and dexamethasone in high dose (Cohort 1) or high dose for 2 cycles, then low dose for 2 cycles (Cohort2). Cycles were 28 days and patients received prophylactic acyclovir and a quinolone antibiotic. Response after 4 cycles was the primary goal and secondary goals were PFS, OS and toxicity of this regimen. Patients were stratified to high risk or standard risk by mSMART criteria. ResultsThe overall response for all patients (n=63) was 89% with 62% VGPR or better. The 5 year PFS and OS rates were 42% (95%CI: 31-57) and 70% (95%CI: 59-82) for the entire group (Figure 1). Twenty-four of the 63 patients were high risk (38%). Patients considered high risk had a lower 5 year PFS (33% (95%CI: 19-59) vs 48% (95%CI: 33-69)) and OS rate (54% (95%CI: 37-78) vs 81% (95%CI: 69-95) compared to standard risk. Most patients underwent auto stem cell transplant after completing the induction trial and most did not utilize maintenance therapy post SCT. ConclusionsEarly and deep responses are needed for long-term disease control in MM. CyBorD maximizes responses and allows for stem cell collection and transplantation which can further consolidate response and improve outcome. This combination is more cost effective than other triplet options while yielding equivalent responses and preserving the opportunity for future IMiD therapy. CyBorD employed in a once weekly schedule is not associated with thrombosis or severe neuropathy. The result is excellent survival for patients with standard risk multiple myeloma. Eighty-one percent of standard risk patients are alive at 5 years. High risk MM patients respond well but survival data confirm the need for ongoing consolidation and or maintenance therapy. CyBorD induction should be considered a standard regimen for transplant-eligible patients with newly diagnosed MM.Ref1 Leukemia 2009; 23(7):1337-13412 Blood 2010; 115(16):3416-34173 Blood 2012; 119(19):4375-4382 [Display omitted] [Display omitted] Disclosures:Reeder:Novartis: Research Funding; Celgene: Research Funding; Millennium: Research Funding. Chen:Celgene: Consultancy, Honoraria, Research Funding. Fonseca:millennium: Consultancy; amgen: Consultancy; Binding site: Consultancy; onyx: Consultancy; medtronic: Consultancy; Genzyme: Consultancy; Otsuka: Consultancy; Celgene: Consultancy; lilly: Consultancy; Onyx: Research Funding; cylene: Research Funding. Bergsagel:Onyx: Consultancy. Tiedemann:Celgene: Honoraria; Janssen: Honoraria. Stewart:Onyx: Consultancy, Research Funding; Millennium: Honoraria, Research Funding; Celgene: Honoraria; BMS: Honoraria.

Dose-Adjusted Rituximab Mini-CYVE (CYtarabine bolus, VEpeside and dexamethasone) for Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma Not Eligible for High Dose Therapy

Background. There is no current standard of care for the management of patients with relapsed or refractory B-cell non-Hodgkin Lymphoma (R/R B-NHL) ineligible for high-dose therapy. While cytarabine and etoposide are commonly used drugs in salvage regiments for patients eligible for high dose therapy (HDT) and auto-stem cell transplant, data are sparse in the context of ineligibility for high-dose therapy. We designed a dose-adjusted combination of rituximab plus mini-CYVE (CYtarabine bolus, VEpeside and dexamethasone) regimen (R-mini-CYVE), for R/R B-NHL patient's ineligible for HDT.Patients and methods. We retrospectively included patients over 60 years old and ineligible for HDT that received R-mini-CYVE regimen for R/R B-cell NHL between January 2009 and November 2015 at Gustave Roussy, Villejuif, France. Patients must be previously treated with anthracycline-containing chemotherapy regimen. Patients could be included regardless of performance status statement and comorbidity. Treatment consisted of combination of intravenously rituximab mini-CYVE given for six to eight cycles every three weeks. All patients received the same doses of rituximab intravenously 375 mg/m2 at day 1, and oral dexamethasone 40 mg/d at days 1-4. Patients received intravenously cytarabine bolus at days 1 and 2 and vepeside at days 1 to 3. Patients were allocated in four dose levels of chemotherapy (cytarabine bolus and vepeside), according to physician discretion among age and comorbidity. Dose levels of cytarabine/vepeside in mg/m2/d were 500/75 for level 1, 1000/75 for level 2, 1000/100 for level 3 and 1500/100 for level 4. Patients were assessed for response after two cycles and at the end of treatment, by computerized tomography scan according to the international harmonized project Cheson 1999 criteria. Primary endpoints were overall survival, and overall response rate (ORR) at the end of treatment. Toxicity was registered according to the CTCAEv4.03.Results. Thirty-seven patients (21 men and 16 woman) received at least one cycle of rituximab mini-CYVE treatment. Among them, the reasons for no eligibility to HDT were a poor performance status over 2 (n=28), renal impairment with glomerular filtration rate below 60 ml/min (n=7), hearing impairment (n=2). Histological types were diffuse large B-cell lymphoma in 31/37 (84 %) patients and indolent B-cell NHL in 6/37 (16 %) patients. At inclusion, median age was 75 [61-88] years old, median number of prior therapies lines was 1 [1-5], Ann-Arbor stage was 3 or 4 in 28/37 (76%) and serum lactate dehydrogenase was increase in 19/37 (51%) patients. Thirteen, 9, 8 and 7 patients received the dose levels 1, 2, 3 and 4, respectively. Median number of cycles was 4 [1-8]. Hematological adverse events grade 3-5 were experienced in 26/37 (70%) patients, and non-hematological grade 3-4 adverse event in 7/37 (19%) patients. One patient died from febrile neutropenia grade 5 during treatment. Non-hematological grade 3-4 adverse events were sepsis in 6/37 (16%) patients and acute cerebellar syndrome related to aracytine at dose level 2 in 1/37 (3%) of patients. Adverse events led to treatment discontinuation in 4/37 (11 %) of pts. ORR was 43% (16/37 pts) including 35% (13/37 pts) of CR or CRu and 8% (3/37) of PR. Median OS and PFS were 13.2 (95% C.I, 9.8-16.6 months), and 6.4 (95% C.I, 1.2 - 11.5) months. With a median follow-up of 12 [range 1 to 60] months, 25/37 patients (67%) had died from progressive disease (n=21), sepsis (n=3) or pulmonary embolism (n=1).Conclusion. The dose-adjusted rituximab mini-CYVE regimen demonstrated a favorable safety and efficacy profile in R/R B-cell NHL patients not eligible for high-dose chemotherapy. Further studies are warranted to investigate this regimen in this population of patients. DisclosuresRibrag:BMS: Honoraria; Roche: Honoraria; Infinity: Honoraria; MSD: Honoraria; Nanostring: Honoraria; Gilead: Honoraria; Servier: Consultancy, Honoraria; ArgenX: Research Funding; Epizyme: Honoraria.

Crizotinib in Advanced ALK+ Anaplastic Large Cell Lymphoma in Children and Adults: Results of the Acs© Phase II Trial

Background:Crizotinib (czb) has shown significant clinical activity in relapsed/refractory ALK+ ALCL in small cohorts of patients (pts) but this drug has yet to be approved for the treatment of these pts in Europe. To avoid off-label use and allow for a nationwide access to czb for pts with ALK+ tumor including ALK+ ALCL, the French National Cancer Institute (INCa) launched the AcSé program, funding both access to tumor molecular diagnosis and an exploratory multi tumor phase II trial. We report the results of the ALCL cohort.Methods:All pts > 1 year (yr) of age with advanced ALK+ ALCL and measurable disease who were not amenable to curative treatment could be included in the trial providing they had adequate hematologic, renal and hepatic functions and had recovered from toxicities of previous treatment (Tt).A two-stage Simon design was planned with a 90% power to detect an objective response rate at 2 cycles (completed response (CR) + partial response (PR)) above 40% against a 20% rate at the 10% level. Responses were assessed every 8 weeks. All imaging were centrally reviewed.Dose of czb was 250 mg BID in adults and 165 mg/m2 BID in children.Results:Among 17 pts enrolled from Feb. 2014 to June 2017, 2 did not receive czb (one early death before the first czb administration and one consent withdrawal) and 15 are evaluable for response. Median age is 21 yr (1-60 yr) with 6 pts under age 18. The median number of prior chemotherapy lines was 2 including brentuximab in 10 pts (66%) and a stem cell autotransplant in 3 pts. Seven pts were had refractory ALCL as defined by disease progression during frontline Tt, 6 were enrolled after one or several relapses with a median time between end of Tt and 1st relapse of 3.5 months (m) and 2 critically ill pts were included for frontline Tt after failure of steroid based prephase.Among the 15 evaluable pts, 10 achieved an objective response (67%, CI95% [42%-85%]) (9CR, 1PR) and 5 experienced a disease progression. The response rate was similar in pts under 18 (4/6, 67%, CI95% [24%, 94%]) and in adults (6/9, 67%, CI95% [31%, 91%]).The median duration of Tt was 3.7 m for the entirecohort and 6.5 m for pts who achieved a response (20 d - 23 m); 2 pts remained on Tt for more than 11 m at the date of last follow-up and 13 have stopped czb (5 for progression, 5 for alloSCT, 3 for maintenance with other drugs). All tumor progressions during czb Tt occurred within 3 m from Tt and 3/5 occurred in pts with refractory disease. Among the 10 pts who achieved a response, 3/8 progressed after czb discontinuation and 7 remain in complete remission.With a median follow-up of 12 m, the median progression free survival is 11.6 m (CI95% [1.41, NA]).Overall 4 pts died and 11 are still alive.Czb was well tolerated with 5 grade (gr) ≥ 3 AEs; one patient with gr 3 hematological toxicities and one patient with gr 3 cytolysis. The mainAEs related to czb were gr 1 (75% of AE), including nausea/vomiting (15%), elevated transaminases (11%), visual disorders (11%).ConclusionCrizotinib proved well tolerated and able to induce durable objective responses in most ALCL pts. During crizotinib treatment all progressions occurred during the first 3 months. DisclosuresMorschhauser:Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Servier: Consultancy; Gilead: Consultancy.

Outcomes, Toxicities, and Patterns of Use of Programmed Death-1 (PD-1) Inhibitors in Hodgkin Lymphoma Patients in the United States: A Multicenter Retrospective Study

Outcomes, Toxicities, and Patterns of Use of Programmed Death-1 (PD-1) Inhibitors in Hodgkin Lymphoma Patients in the United States: A Multicenter Retrospective Study

Immune polychemotherapy regimen choice in B-cell non-Hodgkin lymphoma of high and low malignancy based on the identification of the mutational c-myc and BCL 2 genes

Introduction: The relevance of research is conditioned by the study of the gene expression profile for the identification of molecular subgroups of non-Hodgkin B-cell lymphomas (NHBCLs) in haematology. Aim: The aim of this research was to study the gene expression profile with the identification of molecular subgroups in patients with NHBCLs for personalised treatment. Material and methods: This paper is aimed at analysing the frequency and role of expression of c-myc, B-cell lymphoma 2 (BCL 2) proteins and the Ki 67 proliferative index in patients with NHBCLs and conducting personalised therapy to improve the immediate effectiveness and immediate treatment results. Results and discussion: The paper presents the results of the use of high-dose polychemotherapy (PCT) in 9 patients out of 80 with NHBCL during co-expression of the c-myc, BCL 2 mutational gene and with high values of the Ki 67 proliferative index. High-dose chemotherapy (HDCT) was performed according to the R+HyperCVAD scheme (6 courses) and hematopoietic stem cell (HSC) autotransplantation improved the immediate effectiveness of therapy, with a complete remission rate of 80% and an event-free survival of 28 months. Conclusions: The study of molecular genetic characteristics in 80 patients with NHBCLs revealed co-expression of the c-myc and BCL 2 mutational gene in 9 out of 80 patients, and they differed in the aggressive course, ‘poor’ response to therapy, which predetermined the use of high-dose PCT with transplantation of autologous stem cells.

A phase 1b study of once‐weekly carfilzomib combined with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma

Twice‐weekly carfilzomib with lenalidomide‐dexamethasone (Rd) is an effective regimen for newly diagnosed multiple myeloma (NDMM). Here we evaluated once‐weekly carfilzomib with Rd (once‐weekly KRd) in NDMM patients. The NDMM patients were enrolled regardless of transplant eligibility. Patients received carfilzomib on days 1, 8, and 15; lenalidomide 25 mg on days 1‐21; and dexamethasone 40 mg on carfilzomib days (also day 22 for cycles 1‐8) for ≤18, 28‐day cycles. Enrollment initiated in a carfilzomib 20/70 mg/m2 (20 mg/m2 on cycle one, day 1; 70 mg/m2 thereafter) NDMM dose‐expansion arm, which was suspended because of serious adverse events. After evaluation of dose‐limiting toxicities in a two‐step‐up dose‐evaluation cohort, an NDMM dose‐expansion arm (carfilzomib 20/56 mg/m2) was opened. Fifty‐one NDMM patients were enrolled in dose‐finding and dose‐expansion cohorts. Results are presented for the carfilzomib 56 mg/m2 NDMM dose‐expansion arm (n = 33). The grade ≥ 3 treatment‐emergent AE (TEAE) rate was 63.6%. Twenty‐five patients underwent stem cell collection; 18 proceeded to auto stem cell transplant, and five resumed KRd on study after autoSCT. The overall response rate (ORR) based on best overall response by cycle four was 97.0% (≥very good partial response [VGPR], 69.7%) in the NDMM 20/56 mg/m2 cohort. In patients who did not receive autoSCT (n = 15), the median number of cycles was 16.0; ORR was 93.3% (≥VGPR, 80.0%). At a median follow‐up of 8.1 months, median progression‐free survival was not reached. Once‐weekly KRd (carfilzomib 56 mg/m2) had a favorable safety profile and promising activity in NDMM, supporting the use of this regimen in this setting.

Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial

AbstractIn the European Organization for Research and Treatment of Cancer Leukemia Group and Gruppo Italiano Malattie Ematologiche dell’ Adulto (EORTC-LG/GIMEMA) acute myeloid leukemia (AML)–10 trial, patients in first complete remission (CR1) received a single intensive consolidation (IC) course. Subsequently, those patients younger than 46 years with an HLA-identical sibling donor were assigned to undergo allogeneic (allo) stem cell transplantation (SCT), and patients without such a donor were planned for autologous (auto) SCT. Between November 1993 and December 1999, of 1198 patients aged younger than 46 years, 822 achieved CR. The study group constituted 734 patients who received IC: 293 had a sibling donor and 441 did not. Allo-SCT and auto-SCT were performed in 68.9% and 55.8%, respectively. Cytogenetic determination was successfully performed in 446 patients. Risk groups were good (t(8;21), inv16), intermediate (NN or –Y only), and bad/very bad (all others). Median follow-up was 4 years; 289 patients relapsed, 66 died in CR1, and 293 died. Intention-to-treat analysis revealed that the 4-year disease-free survival (DFS) rate of patients with a donor versus those without a donor was 52.2% versus 42.2%,P= .044; hazard ratio = 0.80, 95% confidence interval (0.64, 0.995), the relapse incidence was 30.4% versus 52.5%, death in CR1 was 17.4% versus 5.3%, and the survival rate was 58.3% versus 50.8% (P= .18). The DFS rates in patients with and without a sibling donor were similar in patients with good/intermediate risk but were 43.4% and 18.4%, respectively, in patients with bad/very bad risk cytogenetics. In younger patients (15-35 years), the difference was more pronounced. The strategy to perform early allo-SCT led to better overall results than auto-SCT, especially for younger patients or those with bad/very bad risk cytogenetics.

Is Molecular Characterization Useful for Targeted Therapy Orientation in Patients with Relapsed or Refractory DLBCL Included in Early Phase Clinical Trials?

Is Molecular Characterization Useful for Targeted Therapy Orientation in Patients with Relapsed or Refractory DLBCL Included in Early Phase Clinical Trials?

Epidemiology and Clinicopathology of Hepatosplenic T-Cell Lymphoma (HSTCL): Analysis of a Pooled Database

Introduction: HSTCL is a rare and rapidly progressive extranodal T-cell lymphoma. It accounts to for 1-2% of all T/NK cell lymphomas. Afflicting adolescents and younger adults, HSTCL commonly presents with constitutional symptoms, cytopenias, and hepatosplenomegaly. Up to a third of all the reported cases arise within a clinical context of immunosuppression. This analysis was conducted to update and expand our existing knowledge of this rare disease. Methods: In order to study the demographic characteristics, cytogenetic and molecular signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 360 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathology factors on overall survival (OS). Results: A total of 360 patients with confirmed HSTCL were identified. The median age was 30 (0.8-86) years with a peak incidence between ages 13 and 26. There is male predominance with M:F ratio of 2.6 in the whole group, 6 in the immunosuppressed, 2.2 in γδ, and 1.2 αβ. HSTCL with TCRαβ tended to be more CD5+, CD8+, and CD57+. More than 90% presented with constitutional symptoms and had bone marrow involvement. Median overall survival of the whole group was 12 months. The median duration of symptoms to diagnosis is 2 months. The median time from immunosuppression to diagnosis is 5.3 years. Sex, age, jaundice, autoimmune hemolytic anemia, hemophagocytosis, and bone marrow involvement did not affect OS. Furthermore, i7 and/or +8 and TCR type did not impact OS. Compared to no treatment, combination chemotherapy and auto and allo stem cell transplant (SCT) were statistically superior with a median OS of 1, 9, 34, and 30 months respectively. While OS of combination chemotherapy was inferior to that of SCT, there was no significant difference between auto and allo SCT. Immunosuppression adversely impacted OS in the whole group (HR:0.40, p&amp;lt;0.0001) and among the SCT subgroup (HR:0.38, p=0.06). There was no difference between immunosuppression with and without TNFα inhibitors. The quality of response prior to transplant also seemed to impact outcome though it did not reach statistical significance (p=0.07) with OS of 15, 30, and 44 months for none/transient, response less than CR, and CR respectively. Splenectomy improved survival in the whole group (HR:0.66; 95%CI 0.47-0.93). Further analysis revealed that splenectomy impacted survival in the context of combination chemotherapy but not SCT. Conclusions: This study presents an updated epidemiologic and clinicopathologic data from a pooled cohort of patients with HSTCL. It identifies the impact of immunosuppression, quality of response, treatment modalities as well as splenectomy on OS. Disclosures No relevant conflicts of interest to declare.