Analysis of Pre-Transplant Therapy with Brentuximab Vedotin for Relapsed/Refractory Hodgkin Lymphoma on Outcomes of Reduced Intensity Conditioned Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4406-4406 ◽  
Author(s):  
Baldeep Wirk ◽  
Barry E. Storer ◽  
David G Maloney ◽  
Ajay K Gopal ◽  
Ryan D Cassaday ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Brentuximab Vedotin ◽  
Prior History ◽  
Prior Therapy ◽  
History Of ◽  
The Impact ◽  
Refractory Hodgkin Lymphoma

Abstract Background: The impact of prior salvage therapy with brentuximab vedotin (BV) for relapsed/ refractory Hodgkin lymphoma (HL) on long-term outcomes after reduced intensity conditioned (RIC) allogeneic hematopoietic cell transplantation (allo-HCT) is unknown. Early studies (Chen et al Biol Blood Marrow Transplant 2014; 20: 1864-1868) suggested an improved 2-year progression free survival (PFS) with BV salvage given before allo-HCT compared to patients without prior BV treatment. In the current study, we analyzed the impact of prior therapy on the incidence of chronic graft-versus-host disease (cGVHD) and other major outcomes in patients, who received an RIC allo-HCT for relapsed HL. Methods: This is a retrospective study of relapsed/refractory HL patients who had RIC allo-HCT between 2005-2014 at the Fred Hutchison Cancer Research Center. Patients were grouped according to prior history of salvage therapy with or without BV pre allo-HCT. Baseline patient characteristics are shown in the Table. Results: Of the 62 consecutive allo-HCT recipients in this study, 25 had prior therapy with BV (BV group) and 37 received other chemotherapy alone (No BV group) for relapsed HL before allo-HCT. More patients in the BV group were in complete remission at allo-HCT (Table). The 100 day acute GVHD and 5 year cGVHD incidence for the BV vs. no BV group were 58% (95% confidence intervals [CI]: 39%-78%) vs. 65% (95% CI: 50%-80%), p=0.6 and 46% (95% CI: 26%-67%) vs. 51% (95% CI: 35%-68%), p=0.66, respectively. The 5 year non-relapse mortality and relapse/ progression for the BV vs. no BV group were 8% (95% CI: 1%-19%) vs. 25% (95% CI: 11%-38%), p=0.13 and 46% (95% CI: 24%-67%) vs. 38% (95% CI: 22%-53%), p0.98. The 5 year PFS and overall survival for BV vs. no BV group were 46% (95% CI: 25%-68%) vs. 38% (95% CI: 22%-53%), p=0.44 and 78% (95% CI: 60%-95%) vs. 56% (95% CI: 40%-72%), p=0.14. The major cause of death in both groups was relapsed HL. Conclusion: With longer follow-up, similar incidences of cGVHD, PFS and OS were observed in patients who received salvage therapy for relapsed/refractory HL prior to allo-HCT with or without BV. Any potential differences in cGVHD and other major outcomes need to be tested in a larger population. Table 1. Characteristics Prior treatment with Brentuximab vedotin Yes N=25 No N=37 Median age, years (range) 27 (14-47) 32 (17-64) Disease stage at diagnosis, n (%) I II III IV 2 (8)11 (44)7 (28)5 (20) 0 (0)15 (41)12 (32)10 (27) Prior history of local radiation pre allo-HCT 20 (80) 29 (78) No. of prior lines of therapies pre allo-HCT 4 (2 - 10) 3 (2 - 7 ) Prior autologous HCT, n (%) 0 1 2 (tandem auto) 1 (4) 21 (84) 3 (12) 0 (0) 35 (96) 2 (4) Disease status at allo-HCT, n (%) Complete remission Partial remission Progressive disease 9 (36) 13 (52) 3 (12) 7 (19)20 (54)10 (27) Median interval from diagnosis to allo-HCT, months (range) 33 (10.7-222) 30.7 (5-292) Graft type, n (%) Bone Marrow Peripheral blood stem cells 9 (36) 16 (64) 15 (41) 22 (59) Donor type, n (%) Haploidentical Matched related Matched unrelated Mismatch unrelated 16 (64) 5 (20) 4 (16) 0 (0) 17 (46) 14 (38) 5 (14) 1 (2) Conditioning for allo-HCT, n (%) FLU/CY/TBI (2 Gy) FLU/TBI (2 Gy) FLU/TBI (3 Gy) TBI (2 Gy) 16 (64) 6 (24) 1 (4) 2 (8) 17 (46) 15 (40) 0 (0) 5 (14) GVHD prophylaxis, n (%) CNI/MMF/post transplant CY CNI+MMF+/- other 16 (64) 9 (36) 17 (46)20 (54) Median follow-up, months (range) 34 (4 - 99) 84 (34 - 121) Abbrev: FLU fludarabine, CY cyclophosphamide, TBI total body irradiation,CNI calcineurin inhibitor, MMF mycophenolate mofetil Disclosures Maloney: Seattle Genetics: Honoraria; Roche/Genentech: Honoraria; Janssen Scientific Affairs: Honoraria; Juno Therapeutics: Research Funding. Gopal:Gilead, Spectrum, Pfizer, Janssen, Seattle Genetics: Consultancy; Spectrum, Pfizer, BioMarin, Cephalon/Teva, Emergent/Abbott. Gilead, Janssen., Merck, Milennium, Piramal, Seattle Genetics, Giogen Idec, BMS: Research Funding; Millennium, Seattle Genetics, Sanofi-Aventis: Honoraria. Cassaday:Seattle Genetics: Research Funding; Pfizer: Research Funding. Sandmaier:Gilliad: Honoraria; ArevaMed: Honoraria; Jazz Pharmaceutical: Honoraria; Seattle Genetics: Honoraria; Abmit: Research Funding; Bellicum: Research Funding.

scholarly journals Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients

2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Flaminia Olearo ◽  
Huyen Nguyen ◽  
Fabrice Bonnet ◽  
Sabine Yerly ◽  
Gilles Wandeler ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Antiviral Treatment ◽  
Composite Endpoint ◽  
Hiv Treatment ◽  
Hiv Positive ◽  
Prior History ◽  
History Of ◽  
The Impact ◽  
Hiv 1

Abstract Objective The impact of the M184V/I mutation on the virological failure (VF) rate in HIV-positive patients with suppressed viremia switching to an abacavir/lamivudine/dolutegravir regimen has been poorly evaluated. Method This is an observational study from 5 European HIV cohorts among treatment-experienced adults with ≤50 copies/mL of HIV-1 RNA who switched to abacavir/lamivudine/dolutegravir. Primary outcome was the time to first VF (2 consecutive HIV-1 RNA >50 copies/mL or single HIV-1 RNA >50 copies/mL accompanied by change in antiretroviral therapy [ART]). We also analyzed a composite outcome considering the presence of VF and/or virological blips. We report also the results of an inverse probability weighting analysis on a restricted population with a prior history of VF on any ART regimen to calculate statistics standardized to the disparate sampling population. Results We included 1626 patients (median follow-up, 288.5 days; interquartile range, 154–441). Patients with a genotypically documented M184V/I mutation (n = 137) had a lower CD4 nadir and a longer history of antiviral treatment. The incidence of VF was 29.8 cases (11.2–79.4) per 1000 person-years in those with a previously documented M184V/I, and 13.6 cases (8.4–21.8) in patients without documented M184V/I. Propensity score weighting in a restricted population (n = 580) showed that M184V/I was not associated with VF or the composite endpoint (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.35–4.59 and HR 1.66; 95% CI, 0.81–3.43, respectively). Conclusions In ART-experienced patients switching to an abacavir/lamivudine/dolutegravir treatment, we observed few VFs and found no evidence for an impact of previously-acquired M184V/I mutation on this outcome. Additional analyses are required to demonstrate whether these findings will remain robust during a longer follow-up.

Skin Cancers Among Chronic Lymphocytic Leukemia (CLL) Patients - the Effect of UV Radiation and CLL Clinical Characteristics

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4772-4772 ◽  
Author(s):  
Geffen Kleinstern ◽  
Abdul Rishi ◽  
Sara J Achenbach ◽  
Kari Rabe Chaffee ◽  
Neil E. Kay ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Uv Radiation ◽  
Mayo Clinic ◽  
Research Funding ◽  
Sun Exposure ◽  
Prior History ◽  
Skin Cancers ◽  
History Of ◽  
Very High

Abstract Background: It is well established that the incidence of skin cancers in patients with CLL are significantly elevated compared to age- and sex- matched controls. However, little is known about the characteristics of CLL patients who develop skin cancer. Herein, we evaluate the associations of CLL clinical and prognostic characteristics, along with UV radiation exposure, with risk of first skin cancer following CLL diagnosis. Methods: Newly diagnosed CLL patients from Minnesota, Iowa, and Wisconsin were enrolled in the Mayo Clinic case-control study from 2002-2015 and systematically followed in the Iowa/Mayo Lymphoma SPORE. Clinical and prognostic CLL data were obtained from the Mayo Clinic CLL database, and skin cancer clinical data were abstracted from medical records using a standard protocol. The CLL international prognostic index (CLL-IPI) was computed using a weighted average of five independent CLL prognostic factors (IGHV mutational status, serum b2-microglobulin, Rai stage, age, and FISH 17p deletion/TP53 status). Self-reported history of midday sun exposure at various ages (birth to age 12; 13 to 21 years; 22 to 40 years, and 41+ years) was obtained from a risk factor questionnaire. For each age, we asked the extent of mid-day sun as: practically no exposure (under 3 hours per week), little exposure (4-7 hours per week), moderate exposure (8 to 14 hours per week) and extensive exposure (15+ hours per week). Midday sun exposure was modeled as an ordinal covariate. To evaluate associations with risk of skin cancer following CLL diagnosis, we calculated time from date of CLL diagnosis to date of first skin cancer, death, or last known follow-up. We used Cox regression analysis to estimate hazard ratios (HRs) and 95% CIs. CLL treatment was considered a time-dependent covariate. Results: Among 846 CLL patients enrolled, the median age at diagnosis was 63 years (range 28-91), 68% were male, 7% had Rai stage III-IV at diagnosis. Based on the CLL-IPI, 42% were categorized as low risk, 33% as intermediate risk, and 25% as high or very-high risk. 109 CLL cases (13%) had one or more reported skin cancers at or prior to CLL diagnosis. Melanoma was observed in 19 (2%) cases and non-melanoma was in 90 (11%) cases. At a median follow-up of 7 years from CLL diagnosis, 165 patients (20%) had one or more skin cancers after CLL diagnosis. Among these patients, 49 had skin cancer before CLL diagnosis. The most frequent skin cancer was squamous cell carcinoma (59%), followed by basal cell (31%), melanoma (5%), and Merkel cell (1%). 552 (65%) of the 846 patients returned a questionnaire. Significant associations of clinical and prognostic characteristics with risk of first skin cancer were observed for age (HR=1.35 per 10 year increase, 95% CI=1.17-1.56, P<0.001), male sex (HR=1.38, 95% CI 0.98-1.96, p=0.07), prior history of skin cancer (HR=4.19, 95% CI=2.98-5.88, P<0.001), and CLL-IPI (HR=1.26, 95% CI= 1.03-1.54, P=0.026, after adjusting for age, sex, and prior skin cancer). Of note, the risk of first skin cancer in those CLL patients categorized as very high via CLL-IPI had 2.28 fold risk (95% CI 1.02-5.11). Midday sun exposures for each of the ages considered showed no evidence of association with risk of first skin cancer (all P>0.05). 50 CLL patients were treated prior to first skin cancer following CLL diagnosis; we observed no evidence of association between treatment and risk of first skin cancer (HR=1.44, 95% CI= 0.93-1.92, P=0.12). Conclusion: CLL patients who are at an increased risk of skin cancer following CLL diagnosis are those who either have had a prior history of skin cancer or a more aggressive CLL disease at diagnosis, according to CLL IPI. Routine skin cancer screening is currently recommended for CLL patients. Our data suggest that more frequent screening would be particularly important among patients with aggressive CLL and who have a prior history of skin cancer. Unexpectedly, we found no evidence of association of skin cancer risk with UV radiation following CLL diagnosis or with CLL treatment. Further investigation is needed to determine whether other factors increase the risk of skin cancer following CLL diagnosis. Disclosures Shanafelt: Genentech: Research Funding; GlaxoSmithkKine: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Cephalon: Research Funding; Pharmacyclics: Research Funding; Hospira: Research Funding.

scholarly journals Dasatinib or Nilotinib Discontinuation in Chronic Phase (CP)-Chronic Myeloid Leukemia (CML) Patients (pts) with Durably Undetectable BCR-ABL Transcripts: Interim Analysis of the STOP 2G-TKI Study with a Minimum Follow-up of 12 Months – on Behalf of the French CML Group Filmc

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 811-811 ◽  
Author(s):  
Delphine Rea ◽  
Franck E. Nicolini ◽  
Michel Tulliez ◽  
Philippe Rousselot ◽  
Francois Guilhot ◽  
...  
Keyword(s):  
Treatment Duration ◽  
Research Funding ◽  
Prior History ◽  
Molecular Response ◽  
Free Survival ◽  
Advanced Phase ◽  
History Of ◽  
Tki Treatment ◽  
Tki Discontinuation

Abstract Background: Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have revolutionized the prognosis of pts suffering from CML but these drugs are considered as non-definitively curative and current recommendation is to treat pts during their entire lifespan. However, prospective trials such as STIM, TWISTER and EUROSKI suggest that imatinib may be successfully stopped in pts with deep and sustained molecular responses. Here, we report on the feasibility of second generation TKIs discontinuation in the setting of the French STOP 2G-TKI study. Methods: Adult CP-CML pts on dasatinib or nilotinib first line or after imatinib without prior allogeneic transplantation or progression to advanced phase CML were proposed TKI discontinuation when presenting: (1) b2a2 or b3a2 BCR-ABL transcripts subtype, 2) TKI treatment duration for at least 36 months, (3) CMR4.5 achieved and maintained for at least 24 months. The primary objective was treatment-free survival without loss of major molecular response (MMR). After TKI discontinuation, BCR-ABL transcripts were monitored monthly during the first 12 months, every 3 months during the 2ndyear and every 3 to 6 months thereafter. Molecular relapse was defined by MMR loss on a single occasion and triggered TKI reintroduction. Data as of August 1, 2014 are reported in pts with at least 12 months of follow-up (n=52) and median follow-up was 32 months (12-56). Results: Median age was 60 years (34-81) and 61.5% of pts were female. Sokal risk group was low in 58%, intermediate in 23%, high in 13% and unknown in 6%. 2G-TKIs were given after imatinib intolerance in 67% of pts, suboptimal response or resistance to imatinib in 23% and upfront in 10%. Median duration of CML, TKI treatment, 2G-TKI treatment and CMR4.5 was 83 months (36-218), 78 months (36-136), 39 months (19-72) and 28 months (24-64), respectively. Twenty four pts lost MMR after a median time of 4 months (1-38) at last follow-up. Importantly, no loss of CHR or progression to advanced phase CML was observed. The 12- and 24-month probabilities of treatment-free survival without MMR loss were 61.4% (95% CI, 48.1-74.6) and 57% (95% CI, 43.3-70.6), respectively. The majority of relapses occurred within 6 months and in a landmark analysis, pts who were still in MMR without therapy at 6 months had 12- and 24-month probabilities of treatment-free survival without MMR loss of 91.2% (95% CI, 81.6-100) and 84.7% (95% CI, 72.2-97.1), respectively. All pts but 1 who lost MMR restarted 2G-TKI treatment and regained MMR after a median time of 3 months (1-8). Pts in MMR without any therapy (n=28) displayed varying patterns of spontaneous molecular response including stable CMR4.5 in 7 and fluctuations between CMR4.5 and MR4.5, CMR4.5 and MR4, CMR4.5 and MMR in 9, 4 and 4 pts, respectively. Gender, age, prior interferon exposure, 2G-TKI type, treatment duration and duration of CMR4.5 were not found to have any impact on outcome. By contrast, prior history of suboptimal response or resistance to imatinib was associated with a significantly lower chance of successful treatment discontinuation, with a 12-month probability of treatment-free survival without MMR loss of 41.7% (95% CI; 13.8%-69.6%), compared to 67.3% (95% CI, 52.6%-81.8%) in other patients (p=0.04). Conclusions: 2G-TKI could be safely and successfully discontinued in CP-CML pts with long-lasting undetectable BCR-ABL transcripts, especially in those without prior history of suboptimal response or resistance. Most of molecular relapses had an early onset and all were sensitive to 2G-TKI resumption. The recurrence of low levels of detectable residual disease below MMR after 2G-TKI withdrawal did not automatically herald CML relapse and did not preclude the possibility to remain treatment-free. Disclosures Nicolini: Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria. Rousselot:Novartis: Research Funding. Gardembas:BMS: Honoraria. Legros:Novartis, BMS: Honoraria. Etienne:Novartis, BMS,Pfizer, ARIAD Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Connect MM®—the Multiple Myeloma (MM) Disease Registry: Incidence of Second Primary Malignancies (SPM)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4749-4749
Author(s):  
Robert M. Rifkin ◽  
Rafat Abonour ◽  
Jatin J. Shah ◽  
Jayesh Mehta ◽  
Mohit Narang ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Board Of Directors ◽  
Solid Tumor ◽  
Research Funding ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Prior History ◽  
Advisory Committees ◽  
History Of

Abstract Background: Increased rates of SPM have been observed as newer cancer treatments have improved survival over the past 2 decades (Fraumeni et al. NCI, 2006). Higher incidence of specific types of hematologic SPM following MM, especially acute myeloid leukemia and myelodysplastic syndromes, have been reported relative to the general population (Dores et al. NCI, 2006; Mailankody et al. Blood, 2011; Ravazi et al. Blood, 2011; Landgren and Mailankody. Leukemia, 2014). A complex interplay between myeloma-, host-, environmental-, and treatment-related factors likely contributes to the increased incidence of SPM in MM. Connect MM is the first and largest prospective, observational, US-based, multicenter registry designed to characterize patients (pts), treatment patterns, and outcomes in newly diagnosed MM (NDMM) pts. Methods: Between September 2009 and November 2012,a total of 1493 NDMM pts were enrolled from 234 US sites within 2 mos of the first diagnosis of MM. Patient data were collected at baseline and each subsequent quarter using a standardized form. Invasive SPM included hematologic and solid tumor second cancers and non-invasive SPM were defined as non-melanoma skin cancers (NMSC). SPM incidence and incidence rate (IR; number of pts with SPM per 100 patient-yrs [PY]) were calculated for all pts and by exposure to specific treatments, including lenalidomide (LEN). PYs were calculated as the observation period from the start of treatment until the detection of the first reported SPM (per category), death, or end of follow-up (pt lost or data cutoff). Results: As of Dec 10, 2013, SPM data were available for 1493 NDMM pts. The median age was 67 yrs (range, 24-94 yrs), 82% of patients were white and 57% were male. Median follow-up was 29.0 mos (0-49 mos). The median OS of treated pts was 44.4 mos. Fifty pts did not receive treatment and had no SPM reported. A total of 74 of the 1443 treated pts (5.1%) reported SPM. Invasive SPM were observed in 51 pts (3.5%): 37 pts (2.6%) with solid tumors and 14 pts (1.0%) with hematologic SPM. Lung/bronchus and myelodysplastic syndromes were the most frequently reported solid tumor and hematologic SPM respectively. NMSC were reported for 26 pts (1.8%). 3 pts had both an invasive SPM and NMSC. The IRs for invasive, hematologic, and solid tumor SPM by LEN exposure are listed in Table 1. By multivariate analysis, the only significant risk factor for the occurrence of SPM was prior history of invasive malignancy. Demographics (including age, ethnicity, race, and gender), International Staging System stage, family history of myeloma or other cancers, history of smoldering MM or monoclonal gammopathy of unknown significance, or prior radiation therapy were not associated with the occurrence of SPM. Conclusions: This analysis shows that there was no increased risk of invasive SPM in this disease-specific registry of pts with NDMM. The risk of SPM for LEN exposed pts was not greater than that for pts not exposed to LEN. In addition, multivariate analysis indicated the only significant risk factor for SPM was prior history of invasive malignancy. As additional agents are approved for the treatment of MM and the length of pt survival increases, longer prospective observation with expanded enrollment on the registry will better characterize the occurrence of SPM in this pt population. Correlations with risk factors including age, pre-existing MDS, risk status, as well as type and duration of therapy will continue to be investigated. Table 1. Incidence rates (per 100 PYa) by treatment exposure IR per 100 PY (95% CI) SPM LEN-Exposed (n = 977) Non–LEN Exposed (n = 466) Invasive 0.85 (0.61-1.19) 1.16 (0.72-1.86) Hematologic 0.17 (0.08-0.36) 0.47 (0.22-0.99) Solid tumor 0.67 (0.46-0.98) 0.68 (0.36-1.26) NMSC 0.50 (0.32-0.77) 0.41 (0.18-0.91) a PY of exposure is the sum of exposure of all pts. Disclosures Rifkin: Celgene Corp: Consultancy; Millenium: Consultancy; Onyx: Consultancy; Takeda: Consultancy; Amgen: Consultancy. Abonour:Celgene Corp: Honoraria, Speakers Bureau. Shah:Celgene Corp: Consultancy, Research Funding. Mehta:Celgene Corp: Consultancy, Speakers Bureau. Narang:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Terebelo:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Gasparetto:Celgene: Consultancy, Honoraria; Millenium: Honoraria. Thomas:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Toomey:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Hardin:Celgene Corp: Research Funding. Lu:Celgene Corp: Employment. Kenvin:Celgene Corp: Employment. Srinivasan:Celgene Corp: Employment, Equity Ownership. Ricafort:Celgene Corp: Employment. Nagarwala:Celgene Corp: Employment. Durie:Celgene Corp: Expert Board Committee Other; IRC Onyx: Membership on an entity's Board of Directors or advisory committees; DMC Millennium: Membership on an entity's Board of Directors or advisory committees; IRC J&J: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Venetoclax-Based Salvage Therapy for Post-Hematopoietic Cell Transplantation Relapse in Acute Myeloid Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2643-2643
Author(s):  
Michael T Byrne ◽  
Nathalie Danielson ◽  
Adrianne Rasche ◽  
Rachel Hammers ◽  
Kathryn A Culos ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Salvage Chemotherapy ◽  
Infectious Complications ◽  
Advisory Committees ◽  
Refractory Aml

Introduction: AML pts who relapse after allogeneic hematopoietic cell transplantation (HCT) face poor clinical outcomes and short overall survival (OS) (Schmid et al, Blood2012). The delivery of optimal salvage therapy is challenging as some pts do not tolerate high intensity regimens, and lower intensity therapies may not yield sufficient disease control. Favorable responses in older, treatment naïve AML pts with venetoclax (VEN) in combination with low-dose cytarabine (LDAC) or DNA methyltransferase inhibitor (DNMTi) led to its approval. Off-label use in relapsed/refractory AML is increasing (DiNardo et al, Am J Hematol2018; Aldoss et al, Haematologica2018). We retrospectively evaluated the overall response rate (ORR = CR+CRi+PR+MLFS) and report our clinical experience with VEN-based salvage in post-HCT relapsed AML. Methods: After IRB approval, consecutive pts with post-HCT relapsed AML treated with VEN+LDAC or VEN+DNMTi from May 2018 to July 2019 were retrospectively analyzed. Selection of VEN partner and dosing were at the discretion of the treating physician based on institutional guidelines and published prescribing information. Responses were assigned based on the AML IWG criteria. The Kaplan-Meier method was used to describe OS. ORR and treatment complications were summarized via descriptive statistics. Results: 18 pts with post-HCT relapsed AML who received at least 1 cycle of VEN-based salvage chemotherapy were included. Median age at HCT was 64.5 years (range 34.5-73.7 years). Most pts were poor risk: 6/18 pts had an antecedent hematologic malignancy, 12/18 had an abnormal or complex karyotype (CK) prior to HCT, and 4/12 pts with CK also were TP53mut. 15/18 (83.3%) received reduced intensity conditioning and MUD was the predominant graft type (50%). All pts received PBSCs. Additional disease and response characteristics are reported in Fig 1A. Median time from HCT to relapse was 5.5 mos (range: 0.9 to 44.9 mos); 27.8% of pts relapsed within 100 days and 55.6% relapsed within 6 mos of HCT. At relapse, 1 patient had grade 2 aGVHD and 1 had severe, extensive cGVHD. No pts experienced a GVHD flare or progression during treatment. 14/18 (77.8%) of pts were receiving immunosuppressive therapy (IST) at relapse and received VEN concurrently with IST. VEN-based salvage chemotherapy began shortly after confirmed relapse (range: 4-46 days); 4/18 pts received VEN with LDAC and 14/18 were treated with a DNMTi partner. 15/18 pts were evaluable for response. IWG responses were seen in 8 pts with an ORR of 53%. There were 0 CR, 6 CRi, 0 PR, 2 MLFS, 7 pts had progressive disease (4 by BM, 3 by PB, Fig 1B). 3/18 additional pts had a ≥50% reduction in circulating blasts indicating treatment effect but were non-evaluable given lack of surveillance BM biopsy. Pts received a median of 2.5 cycles (range 1-9). 15/18 pts had treatment held or delayed due to fever/infection (7), PB cytopenias (4), combination (3), or non-hematologic toxicity (1). 6/8 pts who achieved a CRi/MLFS had VEN dosing reduced or administered as a single-agent. One patient achieved CRi with dose interruptions lasting ≥3 mos, maintained this response, and subsequently cleared a TP53 mutation. The majority of pts 13/18 (72.2%) experienced infectious complications during treatment: 7 developed bacterial pneumonia (4 associated with sepsis), 4 fungal penumonia, and 2 oral infections (both associated with sepsis). 8/18 pts had active infections at the time of death. Time from HCT or IST status did not appear to impact the frequency or severity of infectious complications. After a median of 2.7 mos of follow up (range 0.6-8.9 mos), the mOS after the start of VEN was 130 days. Consolidation with donor lymphocyte infusion or second HCT is planned for several pts. Conclusions: Transplant related- and disease related-mortality are difficult to disentangle in post-HCT AML relapse making it challenging to ascertain the benefit of therapy. In this cohort, the majority of pts relapsed within 6 mos of HCT and were receving IST at the start of salvage therapy. In spite of this, VEN-based salvage induced meaningful responses. To convert these responses to long term survival benefit, as VEN-based salvage is more widely used in this setting, consideration of immunosuppression and previous marrow injury should inform alternative dosing regimens, careful monitoring for infectious complications in close follow-up, and broad spectrum antimicrobial prophylaxis. Disclosures Byrne: Karyopharm: Research Funding. Dholaria:Celgene: Honoraria. Ferrell:Incyte: Research Funding; Agios: Consultancy; Forma Therapeutics: Research Funding; Astex Pharmaceuticals: Research Funding. Jagasia:Kadmon: Consultancy; Incyte: Consultancy; Janssen: Research Funding. Strickland:Astellas Pharma: Consultancy; Sunesis Pharmaceuticals: Research Funding; AbbVie: Consultancy; Jazz: Consultancy; Kite: Consultancy; Pfizer: Consultancy. Savona:Sunesis: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Patents & Royalties; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm Therapeutics: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Selvita: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: Venetoclax use in relapsed/refractory AML

scholarly journals Brentuximab vedotin enables successful reduced-intensity allogeneic hematopoietic cell transplantation in patients with relapsed or refractory Hodgkin lymphoma

Blood ◽  
2012 ◽  
Vol 119 (26) ◽  
pp. 6379-6381 ◽  
Author(s):  
Robert Chen ◽  
Joycelynne M. Palmer ◽  
Sandra H. Thomas ◽  
Ni-Chun Tsai ◽  
Len Farol ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Brentuximab Vedotin ◽  
Free Survival ◽  
Refractory Hodgkin Lymphoma ◽  
Reduced Intensity

Brentuximab vedotin induces an overall response rate of 75% in patients with relapsed/refractory Hodgkin lymphoma, but its impact on future allogeneic transplantation (allo-HCT) is not known. We retrospectively examined the records of 18 patients with relapsed/refractory Hodgkin lymphoma who were treated on brentuximab vedotin clinical trials to evaluate the efficacy and safety of subsequent reduced-intensity allo-HCT. Seventeen patients had previous autologous transplant; 6 were in complete remission, and 8 were in partial remission before allo-HCT with 12 grafts from unrelated or mismatched donors. The 1-year overall survival was 100%, progression-free survival was 92.3%, and nonrelapse mortality was 0% (median follow-up, 14 months). The incidence of acute GVHD was 27.8% and chronic GVHD was 56.3%. Brentuximab vedotin before reduced-intensity allo-HCT does not appear to adversely affect engraftment, GVHD, or survival and may provide sufficient disease control to enable reduced-intensity allo-HCT.

Evaluation Of Allogeneic Hematopoietic Cell Transplantation (HCT) Outcomes Of One Hundred Thirty-Two Patients With Myelodysplastic Syndrome (MDS) Or Chronic Myelomonocytic Leukemia (CMML) Up To Age Seventy-Five and The Effect Of Pre-Transplant 5-Azacitidine

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2152-2152
Author(s):  
Teresa Field ◽  
Janelle Perkins ◽  
Marcie Tomblyn ◽  
Ryan Hillgruber ◽  
Taiga Nishihori ◽  
...  
Keyword(s):  
Research Funding ◽  
Dna Methyltransferase ◽  
Hematopoietic Cell Transplantation ◽  
Negative Impact ◽  
Statistical Significance ◽  
Advisory Committees ◽  
Unrelated Donors ◽  
Risk Treatment ◽  
The Impact

Abstract HCT is the only known curative treatment for MDS. Treatment with the DNA methyltransferase inhibitor 5-azacitidine (aza) can slow leukemic progression and has been utilized prior to HCT for both tumor debulking and to provide stabilization of the disease during the pre-allograft period. To discern the impact of pretransplant aza treatment on HCT outcomes, we retrospectively analyzed 132 patients (pts) according to pretransplant aza exposure. Patients included those who had a diagnosis of MDS or CMML at any time point in the course of their disease who subsequently received a HCT from a HLA-compatible donor. Eligible patients proceeded to transplant if they had adverse disease features such as elevated IPSS risk, treatment related MDS, progression of disease or refractory disease. Consecutive patients referred for HCT between July 2004 and July 2009 were evaluated. Seventy percent of pts with an identified donor proceeded to HCT. All received a myeloablative HCT using fludarabine and IV-busulfan [targeted to a specific AUC of 3500, 5300, 6000 or 7500]. Graft versus host disease prophylaxis was with tacrolimus plus methotrexate or sirolimus or mycophenolate mofetil. Only those with mismatched donors received antithymocyte globulin. The median age of the 64 allograft pts not receiving preHCT aza (No AZA group) was 56.8 (24.8 –73.5) years (yrs). Thirty-seven (58%) pts were older than 55 yrs. At diagnosis, IPSS risk was Low (n=4), Int-1 (n=23), Int-2 (n=13), High (n=5), not evaluable (n=4) (NE), AML (n=16) and CMML (n=9). Seventeen had treatment related MDS (tMDS) and 18 had AML at one time. Donors included 24 sibling donors (MRD), 29 matched unrelated donors (MUD) and 11 mismatched unrelated donors (mMUD). Median follow-up is 66.2 months (29.7 – 105.7 months). Sixty-eight pts received a median of four (1-12) cycles of aza prior to HCT (YES AZA group). The median age was 57.3 (25.6 – 73.8) yrs. Thirty-nine pts (57%) were older than 55 yrs. At diagnosis, IPSS risk was Low (n=3), Int-1 (n=21), Int-2 (n=21), High (n=12), NE (n=2), AML (n=2) and CMML (n=7). Eighteen had tMDS and 10 had AML at one point. Donors included MRD (n=32), MUD (n=31) and mMUD (n=5). Median follow-up is 53.8 months (24.1 – 103.2 months). Prior to transplant the number of marrow blasts in the No-AZA vs Yes-AZA was: <5% (n=37 vs 36), 5-10% (n=12 vs 14), 11 – 20% (n=9 vs 9), >20% (n=2 vs 3) and CMML (n=4 vs 6). All patients engrafted with no difference in engraftment rates or toxicities between the two groups. Additionally, cumulative incidence of non-relapse mortality and relapse rates at 1 yr/ 3 yrs were similar [NRM: No AZA 20.5/ 37.4% vs Yes AZA 20.7/ 23.9 %; REL: 34.2/ 37.5% vs 26.4/ 32.4%]. At 3 years, the RFS and OS suggest improvement with pretransplant AZA but do not reach statistical significance [RFS: No AZA 26% vs Yes AZA 44.1%; p = 0.14; OS: 30.9% vs 51.4%; p=0.15]. Utilization of pre-HCT 5-azaciticidine is a feasible strategy and doesn’t appear to have any negative impact on HCT outcomes. Given the disease control facilitated by aza it should be offered to patients with high risk MDS coming to transplant. Disclosures: Field: Celgene: Research Funding. Alsina:Millennium: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Lancet:Celgene: Research Funding. List:Celgene: Research Funding. Komrokji:Celgene: Research Funding, Speakers Bureau.

scholarly journals Prolonged Overall Survival (OS) in a Subset of Responders to the Combination of Brentuximab Vedotin (Bv) and Bendamustine (B) in Heavily Treated Patients with Relapsed or Refractory Hodgkin Lymphoma (HL): Results of an International Multi- Center Phase I/II Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2907-2907 ◽  
Author(s):  
Ahmed Sawas ◽  
John Kuruvilla ◽  
Jennifer Kimberly Lue ◽  
Changchun Deng ◽  
Jennifer E Amengual ◽  
...  
Keyword(s):  
Research Funding ◽  
Response Rate ◽  
Phase 1 ◽  
Median Number ◽  
High Dose Chemotherapy ◽  
Brentuximab Vedotin ◽  
High Dose ◽  
Refractory Hodgkin Lymphoma

Abstract Introduction Prognosis for patients who fail to respond to high-dose chemotherapy or progress after high dose chemotherapy and autologous stem cell transplant (ASCT) is particularly poor, with a recent study reporting 71% of patients dying in year 1 and 90% by year 2, with a median -progression survival of 1.3 years [1]. In our study of brentuximab vedotin plus bendamustine (BvB) in patients with relapsed or refractory Hodgkin's lymphoma, we recently reported an overall response rate (ORR) and complete response rate (CR) of 71% and a 32% respectively (N=65) in a heavily treated patient population [2]. Having noted several patients with a progression free survival (PFS) of 1 year or longer, we reviewed all enrolled patients for protracted duration of benefit, raising the question as to whether these patients may have been cured by BvB in the salvage setting. (ClinicalTrials.gov #NCT01657331). Methods Among 65 enrolled patients we identified 23 with a PFS of more than one year after treatment with BvB. Patients had received Bv on Day 1 with B on Days 1 and 2 of a 3-week cycle for up to 6 cycles. In the Phase 1 study 4 dose levels were evaluated: (1) Bv = 1.2mg/kg; B = 70mg/m2; (2) Bv = 1.2mg/kg; B = 80mg/m2; (3) Bv = 1.8mg/kg; B = 80mg/m2; and (4) Bv = 1.8mg/kg; B = 90. Accrual followed a classic Fibonacci dose escalation, with 3 patients being treated at each dose level. Dose Limiting Toxicity (DLT), defined as any CTC version 4 Grade 3 or 4 toxicity led to expansion of the dose cohort. The recommended phase II dose was Bv 1.8 mg/kg on Day 1 and B 90 mg/m2 on Days 1 and 2. The Phase 2 portion of the study accrued an additional 37 patients. Response was assessed by the investigator per Cheson 2007 after cycles 2 and 6. Patients were followed post completion of therapy every 3 month until disease progression and imaging was conducted every 3- 6 months. Study procedures and follow-up were concluded on June 30th 2018. In addition, plasma and serum biomarkers were prospectively collected for correlation with toxicity and response. Results With a median follow-up of 33 months (range 20-58 month) we identified 23/65 patients (43% male) with a median age of 34 years (range, 18-55) who experienced a PFS of 1 year or more. The median number of prior systemic therapies was 3 (range 1-6); with 11 patients having had prior ASCT and 10 patients receiving prior radiation therapy. Median number of BvB cycles administered was 4 (range 2-6). A best response of CR was documented for 17 patients (74%) and partial response (PR) was documented for 6 patients (26%). Consolidation with HDCT-ASCT was performed in 10 patients, 3 of whom received maintenance Bv post-transplant. The median duration of response (DOR), PFS and OS among this group was 28, 32 and 34 months, respectively. All responses are ongoing with no evidence of relapse. Long term survival with no further therapy after a median of 6 cycles of BvB ( range 2-6) was observed in 13 patients (20% of the treated population) (median post-BvB PFS 36 months, range 20-58). Exploratory analysis of the correlation between disease outcome and changes from baseline in select biomarkers demonstrated a significantly lower mean baseline sCD30 level among long term responders (p=0.01). No correlations were noted between other clinical outcome metrics and sCD30, nor with other biomarkers including TARC, CD163, or galectin. Conclusion In this heavily treated population with HL, the combination of BvB represents an effective and tolerable outpatient salvage regimen with long term response and protracted survival among a subset of patients, and raises the prospect that these patients, with a historically poor outcome may be cured with BvB. We intend to follow these patients to obtain additional information on their longer term outcome. ReferencesZagadailov, E.A., et al., Real-world effectiveness of brentuximab vedotin versus physicians' choice chemotherapy in patients with relapsed/refractory Hodgkin lymphoma following autologous stem cell transplantation in the United Kingdom and Germany. Leuk Lymphoma, 2018. 59(6): p. 1413-1419.O'Connor, O.A., et al., Brentuximab vedotin plus bendamustine in relapsed or refractory Hodgkin's lymphoma: an international, multicentre, single-arm, phase 1-2 trial. Lancet Oncol, 2018. 19(2): p. 257-266. Disclosures Kuruvilla: Princess Margaret Cancer Foundation: Research Funding; Merck: Consultancy, Honoraria; Leukemia and Lymphoma Society Canada: Research Funding; Lundbeck: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Honoraria; BMS: Consultancy, Honoraria; Abbvie: Consultancy; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Honoraria; Celgene: Honoraria; Roche: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria. O'Connor:ADC Therapeutics: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding.

scholarly journals Renal Function and Risk of Arterial Thrombotic Events in Patients Positive for Lupus Anticoagulant

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 290-290
Author(s):  
Meaghan Colling ◽  
Florian Posch ◽  
Silvia Koder ◽  
Peter Quehenberger ◽  
Cihan Ay ◽  
...  
Keyword(s):  
Risk Factors ◽  
Renal Function ◽  
Lupus Anticoagulant ◽  
Research Funding ◽  
Prior History ◽  
Thromboembolic Events ◽  
Active Smoking ◽  
History Of ◽  
Prospective Risk

Abstract Background: Patients with lupus anticoagulant (LA) are at risk for arterial and venous thromboembolic events. Recent work suggests that LA positive patients who experience thrombotic events in different vascular beds constitute distinct subgroups. To risk stratify patients, further work is needed to better characterize predictors for thromboembolic events in these subgroups. Aims: The aim of this study was to identify baseline characteristics and laboratory parameters associated with the development of arterial or venous thrombotic events. Methods: Patients with at least 2 previous positive LA tests were serially monitored for thrombotic events within the prospective Vienna Lupus Anticoagulant and Thrombosis Study (LATS). Patients without clinical follow-up were excluded from this analysis. Statistical analysis was performed with RStudio (Version 1.1.442). Results: One-hundred-eighty-seven patients were followed (Table 1) for a median of 11.4 years and 1865 follow-up visits (median visit/patient=9). Fifty-seven prospective thrombotic events (TE), including 27 arterial thrombotic events (ATE) and 30 venous thrombotic events (VTE), were observed. This corresponded to 10-year prospective ATE, VTE and overall thrombosis incidences of 13.9% [95%CI: 8.3, 19.6], 18.8% [12.2, 25.4], and 32.0% [24.1, 39.8], respectively. (Figure 1). Thirty-seven of the 57 events occurred in patients with a prior history of thrombosis ("recurrent thrombosis"). In univariable competing risk analysis, age (subdistribution hazard ratio (SHR) = 1.02, 95% CI: 1.00-1.05, p=0.019), body mass index (BMI, 1.05, 1.00-1.11, p=0.042), history of ATE (3.14, 1.45-6.81, p=0.0038), active smoking (2.16, 1.00-4.62, p=0.049), diabetes (4.16, 1.47-11.8, p=0.0073), VKA use at baseline (0.42, 0.18-0.97, p=0.042), aCL IgM positivity (2.48, 1.05-5.83, p=0.038), aβ 2GPI IgM positivity (2.86, 1.18-6.93, p=0.020), mean platelet volume (1.17, 1.06- 1.30, p=0.0024), creatinine (3.76, 1.32- 10.7, p=0.013), and estimate glomerular filtration rate (eGFR, 0.98, 0.96-0.99, p=0.0011) were associated with prospective risk of ATE (Table 2). Conversely, the prospective risk of VTE was univariably associated only with prior history of VTE (3.26, 1.40-7.68, p=0.0061). After adjusting for traditional arterial thrombotic risk factors (age, sex, BMI, active smoking, diabetes,), history of ATE (SHR = 3.97, 95% CI: 1.71-9.025, p=0.0014), prior history of both ATE and VTE (3.87, 1.06-14.16, p=0.041), creatinine (3.93, 1.22-12.66, p=0.022), and eGFR (CKD-EPI, 0.96, 0.96-0.99, p=0.0037) remained independently associated with prospective risk of ATE (Table 2). In detail, the 10-year cumulative risk of ATE was 24.9% [95%CI: 8.8, 41.0], 15.0% [5.8, 24.2], and 6.7% [2.2, 13.8] in patients with a baseline eGFR less than 60 mL/min/1.73m 2, between 60 and 89 mL/min/1.73m 2, and greater than or equal to 90 mL/min/1.73m 2, respectively (Gray's test, p=0.019, Figure 2). Conclusion: Approximately 14% of patients persistently positive for LA experienced an ATE over 10 years. After adjusting for traditional arterial risk factors, decreased renal function was associated with an increased prospective risk of ATE. Notably, decreased renal function was not associated with development of VTE and the association with ATE was also independent of underlying SLE, LLD, or rheumatic disease (data not shown). Clinically, LA positive patients with decreased renal function may represent a subgroup that might benefit from more aggressive anti-thrombotic therapy or anti-thrombotic prophylaxis. Figure 1 Figure 1. Disclosures Pabinger: Bayer: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Daiichi Sanchyo: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; NovoNordisk: Consultancy, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding.

Solid Tumors in Patients with Chronic Lymphocytic Leukemia Who Received Frontline Lenalidomide Therapy: Distribution and Clinical Outcomes

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5573-5573
Author(s):  
Ahmad Alhuraiji ◽  
Lorenzo Falchi ◽  
Michael Keating ◽  
Zeev Estrov ◽  
Paolo Strati ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Clinical Trials ◽  
Radiation Therapy ◽  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Prior History ◽  
Skin Cancers ◽  
History Of

Abstract Introduction: Patients (pts) with Chronic Lymphocytic Leukemia (CLL) are known to have an increased risk of other cancers. Treatment with lenalidomide has been associated with an increased rate of solid tumors (ST) in pts with multiple myeloma (MM). However, the occurrence of ST in patients with CLL receiving therapy with lenalidomide remains unknown. Methods: We evaluated the development of ST in pts with CLL that received front-line treatment with lenalidomide as monotherapy or in combination with rituximab in clinical trials conducted at our institution. We report the characteristics and timing of ST, as well as patient outcome. All pts enrolled had indication for therapy according to the International Workshop on CLL guidelines and no history of malignancy for three years, with the exception of treated malignancy with indolent behavior such as prostate cancer that was treated with surgery or radiation therapy. Results: One-hundred twenty-one pts were enrolled in two consecutive phase II clinical trials of frontline therapy with lenalidomide (N = 61, 51%) or combination of lenalidomide and rituximab (N = 60, 49%). Baseline pts characteristics are shown in Table 1, median age was 66 yrs and 24% of patients were age 70 or older. At a median follow up after lenalidomide therapy of 41 months (range 1-102+), 7 (6%) pts developed a ST: renal cell carcinoma (RCC, 3 pts), localized breast cancer (LCIS and DCIS, 2 pts), pancreatic adenocarcinoma (1 pt) and colon adenocarcinoma (1 pt) (details are shown in Table 2). The median time interval between receiving lenalidomide-based therapy and the development of ST was 1.5 years (range 0-8.5). At the time of this report, 5 out of 7 pts with ST are alive and cancer-free. Two pts died: 12 months and 18 months after developing ST from progression of pancreatic adenocarcinoma and heart failure, respectively. Since pts with CLL have a high rate of non-melanoma skin neoplasms (NMSC), we also monitored patients for new diagnoses of skin cancers. Seven (6%) additional pts developed NMSC, 4 of these pts had prior history of NMSC. All cases of NMSC were superficial and did not require systemic therapy. Additionally, because of the high median age of this population, we reviewed prior history of malignancies. Eleven (9%) pts had history of ST [prostate cancer (N = 9), bladder cancer (N = 1), RCC (N = 1)]. Twenty-two pts (18%) had skin cancers (NMSC, (N = 21) and 1 pt had history of melanoma. None of them had received chemotherapy, two had radiation therapy [prostate cancer = 1, NMSC (basal cell carcinoma of the nose (1 pt)]. All ST were in remission before starting therapy with lenalidomide for more than 3 years as per the inclusion criteria. Conclusions: Seven cases of ST were observed in our population of 121 pts with CLL that received initial therapy with lenalidomide, after a median follow-up of 3.5 years. The most common neoplasm was RCC followed by in-situ breast cancer. In our limited experience the timing, number and type of malignancies do not appear to mirror what was seen in patients with MM. However, this comparison may be limited by the size of our patient population and length of follow-up. Our group reported the incidence of ST in patients treated with FCR. After a similar follow-up the incidence of second malignancies was similar (5.9%), but the type of malignancies was different, although NMSC remained the most common ST in both experiences. Reporting the incidence of other malignancies in patients with CLL enrolled in large studies, including those of novel targeted agents, will help understanding the expected incidence of ST and how novel treatments modulate such risk. Disclosures Jain: Pharmacyclics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Infinity: Research Funding; Abbvie: Research Funding; Genentech: Research Funding; Incyte: Research Funding; Servier: Consultancy, Honoraria; Novimmune: Consultancy, Honoraria; BMS: Research Funding; Novartis: Consultancy, Honoraria. Thompson:Pharmacyclics: Consultancy, Honoraria.

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