scholarly journals Efficacy of venetoclax plus rituximab for relapsed CLL: Five-year follow-up of continuous or limited-duration therapy

Blood ◽  
2021 ◽  
Author(s):  
Shuo Ma ◽  
John F. Seymour ◽  
Danielle M. Brander ◽  
Thomas J. Kipps ◽  
Michael Y. Choi ◽  
...  
Keyword(s):  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Continuous Exposure ◽  
Duration Of Response ◽  
Long Term Follow Up ◽  
Discontinue Therapy ◽  
Limited Duration

We report long-term follow-up of the phase 1b study of venetoclax and rituximab (VenR) in patients with relapsed chronic lymphocytic leukemia (CLL), including outcomes with continuous or limited-duration therapy. Patients received venetoclax daily (200-600 mg) and rituximab over 6 months, then venetoclax monotherapy. Patients achieving complete response (CR), CR with incomplete marrow recovery (CRi), or undetectable minimal residual disease (uMRD) assessed by flow cytometry (<10-4 cutoff) were allowed, but not required, to discontinue therapy, while remaining on study and could be re-treated with VenR upon progression. Median follow-up for all patients (N=49) was 5.3 years. Five-year rates for overall survival, progression-free survival, and duration of response were 86% (95% CI, 72-94), 56% (40-70), and 58% (40-73), respectively. Of the 33 deep responders (CR/CRi or uMRD), 14 remained on venetoclax monotherapy (continuous therapy), and 19 stopped venetoclax therapy (limited-duration therapy) after a median of 1.4 years. Five-year estimates of ongoing response were similar between continuous (71% [95% CI, 39-88]) or limited-duration therapy (79% [49-93]). Six of 19 patients in the latter group had subsequent disease progression, all >2 years off venetoclax (range, 2.1-6.4). Four patients were re-treated with VenR, with partial responses observed in the 3 evaluable to date. VenR induced deep responses that were highly durable with either continuous or limited-duration therapy. Retreatment with VenR induced responses in patients with CLL progression after discontinuing therapy. Continuous exposure to venetoclax in deep responders does not appear to provide incremental benefit. ClinicalTrials.gov ID: NCT01682616

Consolidation Therapy with Subcutaneous (SC) Alemtuzumab After Fludarabine and Rituximab (FR) Induction Therapy Improves the Complete Response (CR) Rate in Chronic Lymphocytic Leukemia (CLL) and Eradicates Minimal Residual Disease (MRD) but Is Associated with Severe Infectious Toxicity: Final Analysis of CALGB Study 10101.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 210-210
Author(s):  
Thomas S Lin ◽  
Kathleen A Donohue ◽  
John C. Byrd ◽  
Margaret S Lucas ◽  
Eva Hoke ◽  
...  
Keyword(s):  
Residual Disease ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Hematologic Toxicity ◽  
Consolidation Therapy ◽  
Varicella Zoster ◽  
Grade 3

Abstract Abstract 210 Background: Alemtuzumab (Campath-1H) is approved for the treatment of CLL. CALGB sought to determine whether alemtuzumab can improve the CR rate and eradicate MRD after induction chemoimmunotherapy by performing a phase II study administering FR followed by alemtuzumab consolidation to previously untreated, symptomatic CLL patients (pts). We previously reported preliminary toxicity data (Lin et al. ASH 2007) and now report final toxicity and response data. Methods: Pts received fludarabine 25 mg/m2 IV on days 1–5, and rituximab 50 mg/m2 IV on day 1, 325 mg/m2 on day 3, and 375 mg/m2 on day 5 of cycle 1 and then only on day 1 of cycles 2–6, repeated every 28 days for up to 6 cycles. Four months after the last fludarabine dose, pts with stable (SD) or responsive disease by NCI 96 criteria received SC alemtuzumab 3 mg on day 1, 10 mg on day 3, and 30 mg on day 5, and then thrice weekly thereafter for 6 weeks (18 total doses). Pts received standard Pneumocystis (PCP) and Varicella zoster virus prophylaxis and were monitored weekly by PCR for Cytomegalovirus (CMV) viremia. When unacceptable serious infectious toxicity was noted in pts who received alemtuzumab after achieving CR from FR induction, the study was amended so that only PR or SD pts received alemtuzumab after FR. Results: Median age of pts (n=102) was 61 years (range, 23–82), 74% were male, and 30% were Rai stage III/IV. FR was well tolerated; 93% of pts received at least 3 cycles, and 77% completed all 6 cycles. Overall, complete and partial response (OR, CR, PR) rates after FR induction were 90%, 29% and 61%, and 15% were MRD negative by flow cytometry. Fifty-eight pts received alemtuzumab, and 42 (72%) completed the planned 6 weeks of therapy. OR, CR, and PR rates after alemtuzumab (n=58) were 91%, 66% and 26%, and 50% were MRD negative. Twenty-eight of 45 pts (62%) in PR after FR who received alemtuzumab attained CR. Of 11 pts in CR after FR who received alemtuzumab, 5 were MRD negative prior to consolidation and 3 of the other 6 converted to MRD negative afterwards. By intent-to-treat for all patients enrolled, OR, CR, and MRD negativity were attained by 90%, 57% and 42% of pts. With a median follow up of 34 months, median progression free survival (PFS) was 37 months (95% CI, 33–43 months); PFS was 73% and overall survival (OS) 86% at 2 years. Two-year PFS (76% vs 70%, p=0.54) and OS (84% vs 88%, p=0.89) were similar for pts who did and did not receive alemtuzumab. Similarly, there were no differences in PFS or OS among the 30 pts in CR after FR whether or not they received alemtuzumab, although the numbers were small. Grade 3–4 neutropenia and thrombocytopenia were observed in 43% and 19% of pts during alemtuzumab therapy. Grade 3–4 non-hematologic toxicity was observed in 41% of pts, including 19% infections and 19% febrile neutropenia, during alemtuzumab therapy. As we previously reported, 5 pts in CR after FR who received alemtuzumab died from infections (viral meningitis, Listeria meningitis, Legionella pneumonia, CMV and PCP pneumonia), and one pt in PR after FR who received alemtuzumab died of Epstein-Barr (EBV) viremia without evidence of EBV lymphoma. These grade 5 toxicities occurred both during and for up to 7 months after alemtuzumab therapy. Conclusions: Alemtuzumab consolidation improved the CR and MRD negative rates after FR induction. However, alemtuzumab consolidation resulted in significant toxicity, particularly severe infections in pts who achieved a CR after FR induction. Longer follow up is needed to determine if the improved CR and MRD negative rates following alemtuzumab consolidation will eventually result in improved PFS or OS, especially among pts who achieved a PR after FR induction. Disclosures: Lin: GlaxoSmithkline: Consultancy, Employment; Genentech: Consultancy; Bayer: Consultancy. Off Label Use: Use of alemtuzumab as consolidation therapy. Byrd:Genentech: Consultancy, Research Funding. Link:Genentech: Consultancy. Rai:Genentech: Consultancy; Bayer: Consultancy.

scholarly journals Consolidation Therapy With Subcutaneous Alemtuzumab After Fludarabine and Rituximab Induction Therapy for Previously Untreated Chronic Lymphocytic Leukemia: Final Analysis of CALGB 10101

2010 ◽  
Vol 28 (29) ◽  
pp. 4500-4506 ◽  
Author(s):  
Thomas S. Lin ◽  
Kathleen A. Donohue ◽  
John C. Byrd ◽  
Margaret S. Lucas ◽  
Eva E. Hoke ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Serious Infections ◽  
Listeria Meningitis ◽  
Intent To Treat

PurposeTo determine if alemtuzumab consolidation improves response rate and progression-free survival (PFS) after induction chemoimmunotherapy in previously untreated symptomatic patients with chronic lymphocytic leukemia.Patients and MethodsPatients (n = 102) received fludarabine 25 mg/m2intravenously days 1 to 5 and rituximab 50 mg/m2day 1, 325 mg/m2day 3, and 375 mg/m2day 5 of cycle 1 and then 375 mg/m2day 1 of cycles 2 to 6; fludarabine plus rituximab (FR) administration was repeated every 28 days for six cycles. Three months after completion of FR, patients with stable disease or better response received subcutaneous alemtuzumab 3 mg day 1, 10 mg day 3, and 30 mg day 5 and then 30 mg three times per week for 5 weeks.ResultsOverall response (OR), complete response (CR), and partial response (PR) rates were 90%, 29%, and 61% after FR, respectively; 15% of patients were minimal residual disease (MRD) negative. Of 102 patients, 58 received alemtuzumab; 28 (61%) of 46 patients achieving PR after FR attained CR after alemtuzumab. By intent to treat (n = 102), OR and CR rates were 90% and 57% after alemtuzumab, respectively; 42% of patients became MRD negative. With median follow-up of 36 months, median PFS was 36 months, 2-year PFS was 72%, and 2-year OS was 86%. In patients achieving CR after FR, alemtuzumab was associated with five deaths resulting from infection (viral and Listeria meningitis and Legionella, cytomegalovirus, and Pneumocystis pneumonias), which occurred up to 7 months after last therapy. The study was amended to exclude CR patients from receiving alemtuzumab.ConclusionAlemtuzumab consolidation improved CR and MRD-negative rates after FR induction but caused serious infections in patients who had already achieved CR after induction and did not improve 2-year PFS or survival.

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 Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

Leukemia ◽  
2020 ◽  
Vol 34 (7) ◽  
pp. 1875-1884 ◽  
Author(s):  
Nizar J. Bahlis ◽  
Meletios A. Dimopoulos ◽  
Darrell J. White ◽  
Lotfi Benboubker ◽  
Gordon Cook ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Open Label Phase ◽  
Intent To Treat ◽  
Line Of Therapy

Abstract In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse.

Treatment with Fludarabine and Rituximab Produces Extended Overall Survival (OS) and Progression-Free Survival (PFS) in Chronic Lymphocytic Leukemia (CLL) without Increased Risk of Second Malignancy: Long-Term Follow up of CALGB Study 9712.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 539-539 ◽  
Author(s):  
Jennifer A Woyach ◽  
Amy S Ruppert ◽  
Nyla A. Heerema ◽  
Bercedis Peterson ◽  
John G. Gribben ◽  
...  
Keyword(s):  
Single Agent ◽  
Progression Free Survival ◽  
Large Cell ◽  
Lymphocytic Leukemia ◽  
Published Data ◽  
Increased Risk ◽  
Long Term Follow Up ◽  
Sequential Group

Abstract Abstract 539 Introduction: The addition of rituximab to fludarabine-based regimens in CLL has been shown to produce high response rates with extended remissions. The long-term follow-up of these regimens with respect to progression, survival, and development of secondary malignancies has been limited. Patients and Methods: We report the long-term follow up of the chemoimmunotherapy trial CALGB 9712 (Blood 2003;101:6-14). This trial randomized 104 untreated, symptomatic patients to receive either 6 monthly cycles of fludarabine plus rituximab (FR) followed 2 months later by 4 weekly doses of rituximab (concurrent arm) or 6 monthly cycles of single agent fludarabine followed by rituximab consolidation using 4 weekly doses (sequential arm). With a median follow up of 92 months (range: 60-107), we analyzed the updated CALGB database and flow sheets submitted by treating physicians. Results: The overall response rate (ORR) was 84% (95% CI: 77%-91%), with a 90% ORR in the concurrent group (95% CI: 82%-98%) and a 77% ORR in the sequential group (95% CI: 66%-89%). Complete response (CR) was seen in 38% of patients (95% CI: 30%-45%), and partial response (PR) in 46% (95% CI: 38%-54%). The median OS was 85 months (95% CI: 71-95), with 71% of patients alive at 5 years (95% CI: 61%-79%). The median PFS was 37 months (95% CI: 27-45), with 27% progression-free at 5 years (95% CI: 19%-36%). With long-term follow up, the estimated median OS and PFS for the concurrent group were 84 months (95% CI: 57-100) and 32 months (95% CI: 23-55), respectively; the median OS and PFS for the sequential group were 91 months (95% CI: 71-110) and 40 months (95% CI: 23-50), respectively. Patients with del(17p13.1)/del(11q22.3)(18 patients) and unmutated IgVH(43 patients) continue to have an inferior OS (P=0.01 and P=0.04, respectively) and PFS (P=0.03 and P=0.04, respectively) compared to those without these abnormalities. We next assessed the frequency of therapy-related myeloid neoplasms (t-MN) and other cancers occurring after this chemoimmunotherapy regimen. No patient has developed MDS or AML prior to relapse. One patient (1%) developed t-MDS following relapse and receipt of FCR 41 months after completing trial therapy; t-MDS was diagnosed 9 months later. Richter's transformation was noted in three (3%) of the CALGB 9712 patients with large cell (n=2) or Hodgkin lymphoma (n=1). Second malignancies have included localized basal cell or squamous cell skin cancer in 12 (12%) patients whereas 11 (11%) have developed other epithelial malignancies including 4 GI, 3 lung, 3 melanomas, and 1 prostate cancer. Conclusions: Long-term follow up of patients enrolled on CALGB 9712 demonstrates extended OS and PFS with fludarabine plus rituximab, given either concurrently or sequentially, with an estimated 17%(95% CI: 9%-27%) of responders still in remission 8 years later. Looking at other published data, patients treated with FR administered concurrently or sequentially do not appear to have an increased risk of t-MN or second cancers. These long-term data reaffirm that FR is one of several acceptable frontline treatments for symptomatic patients with CLL. Disclosures: Morrison: Genentech: Speakers Bureau.

Long-term follow-up of previously untreated patients (pts) with chronic lymphocytic leukemia (CLL) treated with ofatumumab (OFA) and chlorambucil (CHL): Final analysis of the phase 3 COMPLEMENT 1 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7528-7528
Author(s):  
Fritz Offner ◽  
Tadeusz Robak ◽  
Ann Janssens ◽  
Govind Babu Kanakasetty ◽  
Janusz Kloczko ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Final Analysis ◽  
Lymphocytic Leukemia ◽  
Primary Analysis ◽  
Free Survival ◽  
Anti Cancer ◽  
Long Term Follow Up ◽  
Grade 3

7528 Background: Previously in the COMPLEMENT 1 study, treatment with OFA and CHL in pts with untreated CLL had shown a significant improvement in the progression-free survival (PFS) compared with CHL alone, and was well tolerated. Here, we report the final overall survival (OS) analysis of the 5-year (y) follow-up, updated investigator-assessed PFS and safety from the study. Methods: Untreated pts, not fit for fludarabine-based therapy (due to advanced age or co-morbidities) were randomized 1:1 to OFA+CHL or CHL alone. Pts in OFA+CHL arm received OFA (Cycle 1: 300 mg day (d) 1, 1000 mg d8; subsequent cycles: 1000 mg d1) in addition to CHL (10 mg/m2, d1-7) for 3 to 12 cycles of 28 d each. Pts in CHL arm received CHL only. Results: Overall, 447 pts were randomized to OFA+CHL (n = 221) or CHL (n = 226); 168 (76%) and 164 (73%) pts completed the scheduled treatments, respectively. Baseline characteristics were similar in both arms. The investigator-assessed median PFS was 23.4 months (mos) in the OFA+CHL arm and 14.7 mos in the CHL arm (HR: 0.61 [95% CI 0.49, 0.76], p < 0.001). Median OS could not be estimated for the OFA+CHL arm and was 84.7 mos for the CHL arm (HR: 0.88 [95% CI 0.65, 1.17], p = 0.363). Estimated OS rate (95% CI) at 5 y was 68.5% (61.5%, 74.5%) in the OFA+CHL arm, and 65.7% (58.6%, 71.9%) in the CHL arm. Post-treatment anti-cancer therapy after discontinuation was received by a greater proportion of pts in the CHL (66%) vs. OFA+CHL (56%), and started earlier in the CHL arm (486 d) vs. OFA+CHL (743 d) arm. Overall, 84 (39%) pts in the OFA+CHL, and 99 (44%) pts in the CHL arms died during the study with 5 on-treatment deaths in each group. Grade ≥3 adverse events were seen in 64% and 48% of pts in the OFA+CHL vs. CHL arms, respectively, most common being (≥5% in either arm) neutropenia (26% vs. 15%), thrombocytopenia (5% vs. 10%), pneumonia (9% vs. 5%), and anemia (5% vs. 5%). Conclusions: This 5-y survival follow-up analysis supported the results from primary analysis with an estimated 12% (not significant) and 39% risk reduction in OS and PFS, respectively, in the OFA+CHL arm compared with the CHL arm. No new safety concerns were observed in the OFA+CHL arm. Clinical trial information: NCT00748189.

Nivolumab (NIVO) + low-dose ipilimumab (IPI) as first-line (1L) therapy in microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Two-year clinical update.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4040-4040 ◽  
Author(s):  
Heinz-Josef Lenz ◽  
Sara Lonardi ◽  
Vittorina Zagonel ◽  
Eric Van Cutsem ◽  
M. Luisa Limon ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Low Dose ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Duration Of Response ◽  
Therapy Option ◽  
Grade 3

4040 Background: In the phase 2 CheckMate 142 trial, NIVO + low-dose IPI had robust, durable clinical benefit and was well tolerated as 1L therapy for MSI-H/dMMR mCRC (median follow-up 13.8 months [mo; range, 9–19]; Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up is presented here. Methods: Patients (pts) with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg Q2W + low-dose IPI 1 mg/kg Q6W until disease progression or discontinuation. The primary endpoint was investigator-assessed (INV) objective response rate (ORR) per RECIST v1.1. Results: In 45 pts with median follow-up of 29.0 mo, ORR (95% CI) increased to 69% (53–82) (Table) from 60% (44.3–74.3); complete response (CR) rate increased to 13% from 7%. The concordance rate of INV and blinded independent central review was 89%. Median duration of response (DOR) was not reached (Table). Median progression-free survival (PFS) and overall survival (OS) were not reached, and 24-mo rates were 74% and 79%, respectively (Table). Nineteen pts discontinued study treatment without subsequent therapy. An analysis of tumor response post discontinuation will be presented. Ten (22%) pts had grade 3–4 treatment-related adverse events (TRAEs); 3 (7%) had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + low-dose IPI continued to show robust, durable clinical benefit with a deepening of response, and was well tolerated with no new safety signals identified with longer follow-up. NIVO + low-dose IPI may represent a new 1L therapy option for pts with MSI-H/dMMR mCRC. Clinical trial information: NTC02060188 . [Table: see text]

Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: long-term follow-up of an Eastern Cooperative Oncology Group randomized clinical trial.

1991 ◽  
Vol 9 (5) ◽  
pp. 770-776 ◽  
Author(s):  
B Raphael ◽  
J W Andersen ◽  
R Silber ◽  
M Oken ◽  
D Moore ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Eastern Cooperative Oncology Group ◽  
Lymphocytic Leukemia ◽  
Prolonged Treatment ◽  
Maximal Response ◽  
Oncology Group ◽  
Duration Of Response ◽  
Long Term Follow Up

The Eastern Cooperative Oncology Group (ECOG) conducted a study in which patients with advanced chronic lymphocytic leukemia (CLL) were randomized between a regimen consisting of chlorambucil (30 mg/m2 orally day 1) and prednisone (80 mg orally days 1 to 5) (C + P) administered every 2 weeks and a more intensive regimen of cyclosphosphamide (300 mg/m2 orally days 1 to 5), vincristine (1.4 mg/m2 intravenously [IV] day 1), and prednisone (100 mg/m2 orally days 1 to 5) (CVP) given every 3 weeks. Treatment was continued for up to 18 months to maximal response. Of the 122 eligible patients, 60 received C + P, while 62 received CVP. With a median follow-up of 7 years, there were no significant differences in survival (4.8 v 3.9 years, P = .12), complete remission (CR) rate (25% v 23%; P = .83), or duration of response (2.0 v 1.9 years; P = .78) between C + P and CVP. Toxicity was modest despite the prolonged treatment. The long median survival of 4.1 years for stage III and IV patients is superior to that usually reported. This could stem from continuing treatment to maximal response rather than an increase in intensity of therapy. These results are comparable to those reported with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy by other investigators. The data suggest that intermittent C + P administered to maximal response continues to be the standard treatment approach for advanced CLL.

First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7500-7500 ◽  
Author(s):  
Ian Flinn ◽  
Richard van der Jagt ◽  
Julie E. Chang ◽  
Peter Wood ◽  
Tim E. Hawkins ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Complete Response ◽  
Rank Test ◽  
First Line ◽  
Open Label ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Duration Of Response ◽  
Treatment Naïve

7500 Background: BRIGHT, a phase 3, open-label, noninferiority study comparing efficacy and safety of bendamustine plus rituximab (BR) vs rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine and prednisone (R-CVP) in treatment-naive patients (pts) with indolent non-Hodgkin lymphoma (iNHL) or mantle cell lymphoma (MCL), showed that the complete response rate for first-line BR was statistically noninferior to R-CHOP/R-CVP ( Blood 2014). Pts were monitored for ≥5 years (yr) to assess the overall effect of BR or R-CHOP/R-CVP in a controlled clinical setting. This analysis reports the time-to-event variables of the 5-yr follow-up (FU) study. Methods: Pts with iNHL or MCL randomized to 6-8 cycles of BR or R-CHOP/R-CVP underwent complete assessments at end of treatment, then were monitored regularly. Progression-free survival (PFS), event-free survival (EFS), duration of response (DOR) and overall survival (OS) were compared using a stratified log-rank test. Results: Of 447 randomized pts, 224 received BR, 104 R-CHOP, and 119 R-CVP; 419 entered the FU. The median FU time was 65.0 and 64.1 months for BR and R-CHOP/R-CVP, respectively. The 5-yr PFS rate was 65.5% (95% CI 58.5-71.6) and 55.8% (48.4-62.5), and OS was 81.7% (75.7-86.3) and 85% (79.3-89.3) for BR and R-CHOP/R-CVP, respectively. The hazard ratio (95% CI) for PFS was 0.61 (0.45-0.85; P= .0025), EFS 0.63 (0.46-0.84; P= .0020), DOR 0.66 (0.47-0.92; P= .0134), and OS 1.15 (0.72-1.84; P= .5461) comparing BR vs R-CHOP/R-CVP. Similar results were found in iNHL [PFS 0.70 (0.49-1.01; P= .0582)] and MCL [PFS 0.40 (0.21-0.75; P= .0035)], with the strongest effect in MCL. Use of R maintenance was similar, 43% in BR and 45% in R-CHOP/R-CVP. B was included as second-line in 27 (36%) of the 75 pts requiring therapy who originally received R-CHOP/R-CVP. Comparable safety profiles with expected adverse events were observed in the FU study in BR vs R-CHOP/R-CVP. Conclusions: The long-term FU of the BRIGHT study has confirmed that PFS, EFS, and DOR were significantly better for BR, and OS was not statistically different between BR and R-CHOP/R-CVP. The safety profile was as previously reported. Clinical trial information: NCT00877006.

Subcutaneous daratumumab in patients with multiple myeloma who have been previously treated with intravenous daratumumab: A multicenter, randomized, phase II study (LYNX).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS8553-TPS8553
Author(s):  
Nizar J. Bahlis ◽  
Jeffrey A. Zonder ◽  
Susan Wroblewski ◽  
Ming Qi ◽  
Thomas Renaud ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Similar Efficacy ◽  
Phase 2 ◽  
Open Label ◽  
Duration Of Response

TPS8553 Background: The intravenous (IV) formulation of daratumumab (DARA), a human CD38-targeted monoclonal antibody, is approved in many countries for use as monotherapy in relapsed/refractory multiple myeloma (RRMM) and in combination with standard-of-care regimens in RRMM or newly diagnosed MM. A subcutaneous (SC) formulation of DARA is under investigation in several ongoing studies. In the phase 3 COLUMBA study, DARA SC was shown to be non-inferior to DARA IV, demonstrating similar efficacy and pharmacokinetics, with a significantly decreased rate of infusion-related reactions and reduced administration time. The phase 2 LYNX (MMY2065) study will evaluate the efficacy and safety of retreatment with DARA. Methods: In this ongoing, multicenter, open-label, randomized phase 2 study, ~230 patients (pts) with prior exposure to DARA will be randomized 1:1 to receive carfilzomib and dexamethasone (Kd) ± DARA. Pts must have received 1 to 2 prior lines of therapy (at least one of which included DARA IV), with DARA-based therapy completed ≥3 months prior to randomization. Eligible pts have achieved a partial response or better (IMWG criteria) to DARA-based therapy, with a duration of response of ≥4 months. Pts must not have discontinued DARA due to a related adverse event or received prior treatment with carfilzomib. Pts will receive 20 mg/m2 carfilzomib IV on Day 1 of Cycle 1, escalated to 70 mg/m2 on Days 8 and 15; carfilzomib 70 mg/m2 will be administered on Days 1, 8, and 15 of each 28-day cycle thereafter. Dexamethasone 40 mg will be administered (IV or PO) QW for Cycles 1-9 and then on Days 1, 8 and 15 from Cycle 10 onwards. Pts in the D-Kd group will also receive DARA SC (1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; Halozyme]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter. The primary endpoint is the rate of pts achieving a very good partial response or better. Secondary endpoints include overall response rate, rate of pts achieving complete response or better, progression-free survival, overall survival, overall minimal residual disease-negativity rate, time to next treatment, pharmacokinetics, and safety. Clinical trial information: NCT03871829 .

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