Salvage therapies in transplant-eligible relapsed classic Hodgkin lymphoma, are novel regimens better?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7530-7530
Author(s):  
Sanjal Desai ◽  
Yucai Wang ◽  
Allison Claire Rosenthal ◽  
Craig B. Reeder ◽  
David James Inwards ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Multivariate Models ◽  
Bulky Disease ◽  
Classic Hodgkin Lymphoma ◽  
Significant Difference

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

scholarly journals Brentuximab Vedotin Combined With Chemotherapy in Patients With Newly Diagnosed Early-Stage, Unfavorable-Risk Hodgkin Lymphoma

2021 ◽  
pp. JCO.21.00108
Author(s):  
Anita Kumar ◽  
Carla Casulo ◽  
Ranjana H. Advani ◽  
Elizabeth Budde ◽  
Paul M. Barr ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Response Rate ◽  
Complete Response Rate ◽  
Early Stage ◽  
Progression Free Survival ◽  
Complete Response ◽  
Brentuximab Vedotin ◽  
Newly Diagnosed ◽  
Bulky Disease ◽  
Involved Site Radiotherapy

PURPOSE To improve curability and limit long-term adverse effects for newly diagnosed early-stage (ES), unfavorable-risk Hodgkin lymphoma. METHODS In this multicenter study with four sequential cohorts, patients received four cycles of brentuximab vedotin (BV) and doxorubicin, vinblastine, and dacarbazine (AVD). If positron emission tomography (PET)-4–negative, patients received 30-Gy involved-site radiotherapy in cohort 1, 20-Gy involved-site radiotherapy in cohort 2, 30-Gy consolidation-volume radiotherapy in cohort 3, and no radiotherapy in cohort 4. Eligible patients had ES, unfavorable-risk disease. Bulk disease defined by Memorial Sloan Kettering criteria (> 7 cm in maximal transverse or coronal diameter on computed tomography) was not required for cohorts 1 and 2 but was for cohorts 3 and 4. The primary end point was to evaluate safety for cohort 1 and to evaluate complete response rate by PET for cohorts 2-4. RESULTS Of the 117 patients enrolled, 116 completed chemotherapy, with the median age of 32 years: 50% men, 98% stage II, 86% Memorial Sloan Kettering–defined disease bulk, 27% traditional bulk (> 10 cm), 52% elevated erythrocyte sedimentation rate, 21% extranodal involvement, and 56% > 2 involved lymph node sites. The complete response rate in cohorts 1-4 was 93%, 100%, 93%, and 97%, respectively. With median follow-up of 3.8 years (5.9, 4.5, 2.5, and 2.2 years for cohorts 1-4), the overall 2-year progression-free and overall survival were 94% and 99%, respectively. In cohorts 1-4, the 2-year progression-free survival was 93%, 97%, 90%, and 97%, respectively. Adverse events included neutropenia (44%), febrile neutropenia (8%), and peripheral neuropathy (54%), which was largely reversible. CONCLUSION BV + AVD × four cycles is a highly active and well-tolerated treatment program for ES, unfavorable-risk Hodgkin lymphoma, including bulky disease. The efficacy of BV + AVD supports the safe reduction or elimination of consolidative radiation among PET-4–negative patients.

Prediction of Progression-Free Survival with Brentuximab Vedotin Therapy for Relapsed Hodgkin Lymphoma: A Retrospective Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3086-3086
Author(s):  
Anna Houk ◽  
Ajay K. Gopal ◽  
Edward N. Libby ◽  
Andrei R. Shustov ◽  
Damian J. Green ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Confidence Intervals ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Free Survival

Abstract Introduction: The role of brentuximab vedotin (BV) in Hodgkin Lymphoma (HL) is expanding, but factors predicting progression-free survival (PFS) after BV therapy are poorly defined. Age, tumor bulk, presence of extranodal disease, neutrophil:lymphocyte ratio (ANC/ALC), and lymphocyte:monocyte ratio (ALC/AMC) predict outcome in HL patients (pts) treated with chemotherapy, but their impact on PFS after BV has not been well-studied. Also, among pts with relapsed/refractory HL (rel/ref HL) who progress after BV, efficacy of additional chemotherapy is undefined. To inform patient selection and future clinical trial design with BV, we undertook a retrospective study to identify factors predicting PFS with BV therapy in rel/ref HL, and explore chemotherapy efficacy as salvage after BV failure. Methods: Pts receiving BV since 2009 were identified through pharmacy and research records and studied with IRB approval. Those with rel/ref HL receiving BV before or after transplant without intervening therapy were excluded. Age ≥40 at time, sex, pre-BV PET findings (SUV max, extranodal [EN] involvement, bulk > 5cm), prior therapy (# lines of therapy> median; prior transplant, platinum-containing, radiotherapy), and lab findings (AMC/ALC³4.3, ALC/AMC ratio³1) at time of start of BV were examined for an impact on PFS and OS via log-rank testing of Kaplan-meier projections(JMP 11.0 software). PFS was defined as time from first BV dose to radiographic or clinical progression, initiation of post-BV salvage, or death from any cause. OS was measured from date of first BV dose to death from any cause. Efficacy of salvage therapy for those failing BV was recorded. Results: Of 90 patient receiving BV, 43 met above criteria. Median age was 34 yrs (range 17-80), median # of pre-BV therapies was 3 (range 1-7). 31 (73%) had failed autologous transplant, 10 (23%) had undergone allogeneic transplant, and 20 (46%) received radiotherapy prior to BV. Pre-BV PET staging data was available in 26 pts; post-BV PET was not analyzed in this dataset as response criteria were nonstandardized. BV was administered for a median 6 cycles (range 2-20). Median PFS after BV was 6 mo. (Figure 1) with 4 pts having PFS >4 yrs. At 31 mo. median follow-up, 71% of pts were alive with no plateau in the survival curve. On univariate analysis, age 40 or older at time of BV predicted inferior PFS (p=.03) and inferior OS though 95% confidence intervals were wide (OS by age: Figure 2, p=.02). HR for death for pts age 40 or older was 4 (98% CI .03-2.3, p=.05). No other factor predicted PFS or OS. Among 29 pts who failed BV, OS was 3.4 yrs. 40 chemotherapy regimens were given with 11 responses. Five of 11 pts responded to bendamustine, but median time to progression was 4 mo. Two of 4 responded to gemcitabine as did 3/8 receiving platinum chemotherapy. Conclusions: In this cohort of rel/ref HL pts treated with BV, PFS was 6 mo. overall and inferior among pts 40 yrs or older. OS was also worse in this group, although confidence intervals were wide in both univariate analyses. We confirm and expand upon prior data showing features predicting outcomes in HL after chemotherapy do not clearly apply after BV; and that most pts progress <1 year after single-agent BV with a few durable remissions. Salvage chemotherapy after BV has transient efficacy. Larger studies defining clinical, biologic, and PET-based markers of outcome after BV are needed. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Off Label Use: Brentuximab is approved in HL after failure of autologous stem cell transplant; in this series, some patients received Brentuximab before or when ineligible for an autologous stem cell transplant.. Gopal:Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding; Pfizer: Consultancy, Research Funding; BMS: Research Funding; Gilead: Research Funding; Spectrum: Research Funding; Teva: Research Funding. Shustov:Seattle Genetics, Inc.: Research Funding.

Daratumumab (DARA) maintenance or observation (OBS) after treatment with bortezomib, thalidomide and dexamethasone (VTd) with or without DARA and autologous stem cell transplant (ASCT) in patients (pts) with newly diagnosed multiple myeloma (NDMM): CASSIOPEIA Part 2.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8004-8004
Author(s):  
Philippe Moreau ◽  
Pieter Sonneveld ◽  
Keyword(s):  
Interim Analysis ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Second Primary ◽  
Cell Transplant ◽  
Open Label ◽  
Depth Of Response

8004 Background: D-VTd plus ASCT was approved for transplant-eligible (TE) NDMM based on part 1 of CASSIOPEIA. We report a prespecified interim analysis of CASSIOPEIA part 2: DARA maintenance vs OBS in pts with ≥partial response (PR) in part 1, regardless of induction/consolidation (ind/cons) treatment. Methods: CASSIOPEIA is a 2-part, randomized, open-label, phase 3 study in TE NDMM. Pts received 4 cycles ind and 2 cycles cons with D-VTd or VTd. 886 pts who achieved ≥PR were rerandomized to DARA 16 mg/kg IV Q8W for up to 2 yr (n = 442) or OBS (n = 444) until progressive disease per IMWG. Pts were stratified by ind (D-VTd vs VTd) and depth of response (minimum residual disease [MRD] status and post cons response ≥PR). Primary endpoint was progression-free survival (PFS) after second randomization. This interim analysis assessed efficacy and safety after 281 PFS events. A preplanned hierarchical procedure tested key secondary endpoints: time to progression (TTP), ≥complete response (CR), MRD negativity rates by NGS and overall survival (OS). Results: At median follow-up of 35.4 mo, median PFS was not reached (NR) with DARA and 46.7 mo with OBS (HR 0.53; 95% CI 0.42–0.68; P <0.0001). PFS advantage for DARA was consistent across most subgroups. However, a prespecified analysis showed significant interaction with ind/cons treatment arm ( P< 0.0001). PFS HR for DARA vs OBS was 0.32 (95% CI 0.23–0.46) in the VTd arm and 1.02 (0.71–1.47) in the D-VTd arm. Median TTP was NR for DARA vs 46.7 mo for OBS (HR 0.49; 95% CI 0.38–0.62; P <0.0001). More pts in the DARA vs OBS arm achieved ≥CR (72.9% vs 60.8%; OR 2.17; 95% CI 1.54–3.07; P <0.0001). MRD negativity (in ≥CR pts at 10-5) was 58.6% with DARA vs 47.1% with OBS (OR 1.80; 95% CI 1.33–2.43; P= 0.0001). Median OS was NR in either arm. Most common (≥2.5%) grade 3/4 adverse events (AEs) with DARA vs OBS were pneumonia (2.5% vs 1.4%), lymphopenia (3.6% vs 1.8%), and hypertension (3.0% vs 1.6%). Serious AEs occurred in 22.7% (DARA) vs 18.9% (OBS) of pts; the most common (≥2.5%) was pneumonia (2.5% vs 1.6%). 13 (3.0%) pts discontinued DARA due to an AE. The rate of infusion-related reactions was 54.5% (DARA-naïve pts) and 2.2% (prior DARA pts); 90% were grade 1/2.Second primary malignancies occurred in 5.5% (DARA) vs 2.7% (OBS) of pts. Conclusions: CASSIOPEIA part 2 demonstrated a clinical benefit of DARA maintenance in TE NDMM pts, with significantly longer PFS for DARA vs OBS. With current follow-up, maintenance PFS benefit appeared only in pts treated with VTd as ind/cons. Pts who received D-VTd ind/cons with or without DARA maintenance achieved similar PFS; longer follow-up is needed for PFS2 and OS. DARA significantly increased deeper response and MRD negativity rates vs OBS, and was well tolerated with no new safety signals. Clinical trial information: NCT02541383.

scholarly journals Outcome of Hodgkin Lymphoma after Progression Following Autologous Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2994-2994
Author(s):  
Joseph M. Connors ◽  
Alina S Gerrie ◽  
Maryse M Power ◽  
Kerry J Savage
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Single Agent ◽  
Progression Free Survival ◽  
Brentuximab Vedotin ◽  
Primary Objective ◽  
Initial Diagnosis ◽  
Cell Transplant ◽  
Free Survival

Abstract Background Clinical trials have demonstrated a high level of effectiveness for brentuximab vedotin (BV) for patients with relapsed or refractory classical Hodgkin lymphoma (HL); however, how patients fare in routine clinical practice if their HL recurs after autologous stem cell transplant (ASCT) is less clear. Our primary objective was to characterize overall survival (OS) and progression-free survival (PFS) among a cohort of real-world patients treated with BV after ASCT. The secondary objective was to characterize the outcome of treatment after failure of ASCT or ASCT and BV. Methods We screened the population-based British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database to identify patients with classical HL (excluding lymphocyte predominant HL) who were aged >16 years at initial diagnosis, staged and treated in BC, had primary treatment with ABVD or equivalent chemotherapy, underwent ASCT as part of first treatment for refractory or relapsed disease and relapsed again after ASCT. We excluded patients who have been treated at any time with a checkpoint inhibitor. We determined Kaplan-Meier estimates of overall (OS) and progression free survival (PFS) from the date of the progression that occurred after ASCT and, for those treated with the agent, after subsequent BV. Therapies given in sequence without a pause between therapies were considered part of the same line of therapy. Results Between 1986 and 2015 93 patients experienced recurrence of HL after ASCT. Their median age at initial diagnosis was 30 years and 51% were male. After failure of ASCT 23 (25%) received radiation monotherapy and 61 received chemotherapy (66%), either as a single agent or in various combinations and of these 9 (10%) also received radiation; 6 (6%) received a second transplant (5 allogeneic and 1 repeat ASCT); and 5 refused or were too frail for treatment other than with corticosteroids. The median PFS and OS from the time of relapse after ASCT for these 93 patients were 7.1 (range 0.2-352) and 16.2 months (range 0.2-352), respectively. Of those 93, 17 patients received BV alone or BV+bendamustine at some point following ASCT. The median age of BV-treated patients was 33 years at the time of their original diagnosis and 29% were male. Among those 17 patients, 9 received single agent BV and 8, BV+bendamustine as part of a clinical trial. The median time from ASCT to the start of BV was 27.5 months. Counting ASCT as 2nd line treatment, 10 individuals received BV as 3rd line, 6 as 4th line and 1 as 5th line therapy. For all 17 patients the subsequent median PFS and OS from the time of BV initiation were 5.1 (range 1.5-34.6) and 18.8 months (range 2.4-40.5), respectively. 12 of these patients relapsed again and their subsequent median PFS and OS were 0.6 (range 0.5-29) and 3 (range 0.5-30) months, respectively. All 9 patients who received single agent BV relapsed again at a median of 2 months (range 1.2-9.7); 5 of the 8 patients treated with BV+bendamustine remain in remission 6 to 36 months later. Conclusions These data highlight the poor prognosis for patients with relapsed or refractory cHL, particularly for those whose lymphoma recurs after brentuximab vedotin as well as the highly individualized management of patients whose lymphoma has recurred after ASCT. Future therapies that prevent or significantly delay relapse will help in alleviate the substantial clinical burden due to relapsed and refractory Hodgkin lymphoma. Disclosures Connors: Millennium Takeda: Research Funding; Seattle Genetics: Research Funding; NanoString Technologies: Research Funding; F Hoffmann-La Roche: Research Funding; Bristol Myers Squib: Research Funding.

scholarly journals Therapeutic Updates for Relapsed and Refractory Classical Hodgkin Lymphoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2887
Author(s):  
Timothy J Voorhees ◽  
Anne W Beaven
Keyword(s):  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Standard Of Care ◽  
The United States ◽  
Autologous Stem Cell Transplant ◽  
Salvage Chemotherapy ◽  
Brentuximab Vedotin ◽  
Novel Agents ◽  
Cell Transplant ◽  
T Cell Therapy

Hodgkin lymphoma (HL) is a B-cell malignancy representing approximately one in ten lymphomas diagnosed in the United States annually. The majority of patients with HL can be cured with chemotherapy; however, 5–10% will have refractory disease to front-line therapy and 10–30% will relapse. For those with relapsed or refractory (r/r) HL, salvage chemotherapy followed by autologous stem cell transplant (ASCT) is standard of care, but half of patients will subsequently have disease progression. Relapse following ASCT has been associated with exceedingly poor prognosis with a median survival of only 26 months. However, in recent years, novel agents including brentuximab vedotin (BV) and programmed cell death protein 1 monoclonal antibodies (anti-PD-1, nivolumab and pembrolizumab) have been shown to extend overall survival in r/r HL. With the success of novel agents in relapsed disease after ASCT, these therapies are beginning to show clinically meaningful response rates prior to ASCT. Finally, a new investigation in r/r HL continues to produce promising treatment options even after ASCT including CD30 directed chimeric antigen receptor T-cell therapy. In this review, we will discuss the recent advances of BV and anti-PD-1 therapy prior to ASCT, novel approaches in r/r HL after ASCT, and review active clinical trials.

Second Autologous Stem Cell Transplant (ASCT) as Salvage Therapy for Relapsed Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1170-1170
Author(s):  
Rebecca L. Olin ◽  
David L. Porter ◽  
Selina M. Luger ◽  
Stephen J. Schuster ◽  
Donald Tsai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Treatment Options ◽  
Univariate Analysis ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Response To Therapy ◽  
Cell Transplant ◽  
Significant Difference

Abstract Introduction: Autologous stem cell transplant (ASCT) as part of initial therapy has been shown to prolong survival of patients with multiple myeloma, with some achieving durable complete remission. However, the majority of patients ultimately relapse after ASCT and require salvage treatment. Options for the treatment of such patients have increased significantly over recent years, including not only novel chemotherapeutic and biological agents but also additional ASCTs. We performed a retrospective analysis of our experience with salvage ASCT for multiple myeloma to determine which clinical variables influence outcome. Methods: Between October 1992 and February 2005, we performed 342 ASCTs for multiple myeloma. Twenty-six of these were salvage transplants for relapsed disease after prior ASCT, and all were included in the analysis. Patients who received two planned (tandem) ASCTs were not included. Results: The median age at diagnosis was 47 (range 25–66), and median ISS and DS stages at diagnosis were 1 and 2, respectively. The initial ASCT was melphalan-based in 21/26; six (23%) achieved a complete response (CR) to the initial transplant, and fifteen (58%) achieved a partial response (PR). The median event-free survival (EFS) after the initial transplant was 19.5 months (range 2–60). The median time between initial and salvage ASCT was 2.6 years (range 0.3–7.6). Twenty-two patients (85%) received non-transplant therapy between ASCTs, and the median number of lines of therapy prior to salvage ASCT was 3. At the time of salvage ASCT, the median age was 52.5 (range 28–69). Fourteen patients received melphalan alone, eight received melphalan/TBI, and four received other regimens. Eleven patients (42%) achieved a response to therapy (1 CR, 10 PR). One patient (4%) died of transplant-related toxicity. The median follow-up after salvage ASCT is 12 months (range 0.2–58). Median EFS is 9 months, and median overall survival (OS) is 36 months. The 2-year EFS is 14%, and 2-year OS is 52%. On univariate analysis, both response to and EFS after initial transplant significantly predict improved EFS after salvage transplant (p=0.0008 and p=0.0065 respectively). Both also predict improved OS (p=0.03 and 0.0005 respectively). A greater than 12 month interval between first and second transplant also correlated with OS (p=0.04). There was no significant difference in EFS or OS by preparative regimen. Interestingly, type of response to the salvage transplant (CR/PR or less than PR) did not predict improved EFS or OS. Conclusion: This study suggests that salvage ASCT after relapse from initial ASCT is a feasible therapy for patients with heavily treated multiple myeloma, particularly those with a prolonged response to the first transplant.

A Phase 2 Study Of Single-Agent Brentuximab Vedotin For Front-Line Therapy Of Hodgkin Lymphoma In Patients Age 60 Years and Above: Interim Results

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4389-4389 ◽  
Author(s):  
Christopher A. Yasenchak ◽  
Robert Chen ◽  
Jeff P. Sharman ◽  
Ralph V. Boccia ◽  
Beata Holkova ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Single Agent ◽  
Autologous Stem Cell Transplant ◽  
Brentuximab Vedotin ◽  
Cell Transplant ◽  
Treatment Naïve ◽  
Multi Agent ◽  
Grade 3

Abstract Introduction Hodgkin lymphoma (HL) in patients aged ≥60 years has disproportionately inferior outcomes as compared to HL in younger patients. This can be mostly attributed to treatment-related factors that compromise cure rates. Comorbidities in older patients are associated with higher rates of treatment-related toxicities and can prevent delivery of standard intensity and/or duration of chemotherapy. A retrospective multicenter analysis showed an increased incidence of bleomycin-associated pulmonary toxicity (32%; with a mortality rate of 25%) in HL patients aged ≥ 60 who received ABVD for frontline therapy (Evens 2012). Novel therapeutic approaches with improved efficacy and tolerability are needed for this population. Brentuximab vedotin (ADCETRIS®) is an antibody-drug conjugate that comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E. Robust antitumor activity and acceptable toxicity has been demonstrated in HL patients who relapse after conventional chemotherapy or autologous stem cell transplant. A retrospective analysis of patients aged ≥60 years with relapsed/refractory CD30+ lymphomas across 7 single-agent brentuximab vedotin studies showed antitumor activity and clinical response duration consistent with those observed in younger patients (Fanale 2012). Thus, this ongoing phase 2, single-arm, open-label study was initiated to evaluate the efficacy, safety, and tolerability of brentuximab vedotin as frontline monotherapy for HL patients aged ≥60 years (NCT01716806). Methods The population to be enrolled includes ∼30 treatment-naïve patients with classical HL (Stages I–IV). Eligible patients must be aged ≥60 years, have an ECOG status ≤3, and be ineligible for or have declined conventional chemotherapy. Brentuximab vedotin 1.8 mg/kg is administered every 3 weeks by IV infusion. Patients achieving stable disease (SD) or better can receive up to 16 cycles of treatment, after which therapy can be continued for those experiencing clinical benefit. The primary endpoint is objective response rate (ORR) as assessed by the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Response assessments are performed at Cycles 2, 4, 8, 12, and EOT (including PET at Cycles 2, 8, and EOT). Results Thirteen patients with treatment-naïve classical HL have been enrolled to date. Median age was 75 years (range, 64 to 92) and approximately half of the patients were male (54%). Seven patients (54%) had moderate age-related renal insufficiency at baseline (creatinine clearance ≥30 and<60). Thus far, patients have received a median of 5 cycles of brentuximab vedotin treatment (range, 1 to 11). Four patients discontinued treatment, 2 due to progressive disease, 1 due to a serious adverse event (Grade 3 orthostatic hypotension), and 1 due to patient decision. Of the 11 patients with a response assessment (see table), the ORR was 82% (n=9) and the complete remission (CR) rate was 64% (n=7). For the 10 patients who had interim PET scans after 2 cycles of therapy, the mean decrease in maximum standardized uptake value (SUVmax) between baseline and Cycle 2 was 83%. Cycle 2 PET scans were negative (Deauville Score 1-3) in 36% of patients, and the range of duration of response was 0.1+ to 20.6+ weeks thus far. Treatment-related adverse events (AEs) occurring in ≥15% of patients included neutrophil count decreased, peripheral sensory neuropathy, pruritus, and rash (n=2 each); most events were Grade 1 or 2. Grade 3 treatment-related AEs included neutrophil count decreased, rash, and orthostatic hypotension (n=1 each). No Grade 4 or 5 events have been observed to date. Conclusions In this interim analysis of patients aged ≥60 years with newly diagnosed HL, compelling antitumor activity with single-agent brentuximab vedotin has been demonstrated. To date, a response rate of 82% has been shown in this historically challenging population of patients who either declined or were not eligible for standard chemotherapy. Preliminary safety data demonstrate tolerability in this patient population and the data are consistent with the current safety profile of brentuximab vedotin. Disclosures: Yasenchak: Seattle Genetics, Inc.: Research Funding. Off Label Use: Brentuximab vedotin is indicated for treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates and for the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen. Chen:Seattle Genetics, Inc.: Consultancy, Research Funding, Speakers Bureau, Travel expenses Other. Sharman:Seattle Genetics, Inc.: Research Funding, Travel expenses Other; Genentech: Research Funding; Gilead: Research Funding. Boccia:Seattle Genetics, Inc.: Honoraria, Research Funding. Holkova:Seattle Genetics, Inc.: Research Funding. Rosen:Seattle Genetics, Inc.: Advisory/scientific board membership Other, Honoraria, Research Funding. Friedberg:Seattle Genetics, Inc.: Research Funding. O'Meara:Seattle Genetics, Inc.: Employment, Equity Ownership. Forero-Torres:Seattle Genetics, Inc.: Research Funding, Speakers Bureau.

scholarly journals Comparison of Two Post-Transplant Predictive Indexes: Day 100 is a Better Time-Point for Response Evaluation after Autologous Stem Cell Transplantation in Multiple Myeloma: Ass Retrospective Study

2020 ◽  
Vol 7 (8) ◽  
Author(s):  
Ma’koseh M ◽  
◽  
Sa’deh S ◽  
Halahleh K ◽  
Abu-Jazar H ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Response Evaluation ◽  
Therapeutic Implications ◽  
Significant Difference

In Multiple Myeloma (MM), response to High-Dose Chemotherapy (HDC) and Autologous Stem Cell Transplant (ASCT) has important prognostic and therapeutic implications. Best timing for response evaluation after ASCT is not well studied. Our study evaluated the correlation between response on day 30 and day 100 after ASCT with Progression Free Survival (PFS) and Overall Survival (OS) in 119 MM patients. Median follow-up was 39.8 months. Complete Response (CR) was achieved in 53.8% and 55.5% of patients on D 30 and D 100, respectively. On D30, there was no significant difference in PFS or OS in CR vs. no CR group (35.4 vs. 22.1 months, p: 0.058) and (92.6 months vs. not reached p: 0.96) respectively nor in responders (R) vs. Non-Responders (NR) group (97.8 vs. 47.1 months p: 0.08) and (30.2 vs. 18.9 months, p: 0.09) respectively. While on D100, PFS was significantly better in CR vs. no CR group (33.8 vs. 18.1 months, p: 0.0047) as well as in R vs. NR (30.6 vs. 16.9 months p: 0.015). However, OS was not better in either (92.6 vs. 52.1 months p: 0.46) and (92.6 months vs. not reached p: 0, 88) respectively. In conclusion, after HDC and ASCT for MM, we recommend doing response evaluation on D100 rather than D30 as it better correlates with PFS. Further studies are required to confirm this finding in the era of consolidation and maintenance treatment.

scholarly journals Treatment of relapsed or refractory classical Hodgkin lymphoma with the anti-PD-1, tislelizumab: results of a phase 2, single-arm, multicenter study

Leukemia ◽  
2019 ◽  
Vol 34 (2) ◽  
pp. 533-542 ◽  
Author(s):  
Yuqin Song ◽  
Quanli Gao ◽  
Huilai Zhang ◽  
Lei Fan ◽  
Jianfeng Zhou ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Chinese Patients ◽  
Cell Transplant ◽  
Upper Respiratory Tract ◽  
Phase 2 ◽  
Classical Hodgkin Lymphoma ◽  
Overall Response

Abstract Prognosis is poor for patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) after failure of or who are ineligible for autologous stem cell transplant. We evaluated the efficacy and safety of tislelizumab, an investigational anti-PD-1 monoclonal antibody, in phase 2, single-arm study in Chinese patients with R/R cHL. The primary endpoint was overall response rate as assessed by an independent review committee, according to the Lugano 2014 Classification. Seventy patients were enrolled in the study and received at least one dose of tislelizumab. After median follow-up of 9.8 months, 61 (87.1%) patients achieved an objective response, with 44 (62.9%) achieving a complete response (CR). The estimated 9-month progression-free survival rate was 74.5%. Most common grade ≥3 adverse events (AEs) were upper respiratory tract infection and pneumonitis. Infusion-related reactions occurred in 27 (38.6%) patients, and 27 patients (38.6%) experienced an immune-related AE, the most common of which was thyroid dysfunction. Eleven (15.7%) patients experienced at least one treatment-emergent AE leading to dose interruption or delay. No deaths occurred due to AEs. Treatment of patients with R/R cHL with tislelizumab was generally well tolerated and resulted in high overall response and CR rates, potentially translating into more durable responses for these patients.

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