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.

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]

scholarly journals Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION)

Blood ◽  
2014 ◽  
Vol 123 (4) ◽  
pp. 494-500 ◽  
Author(s):  
Elias Jabbour ◽  
Hagop M. Kantarjian ◽  
Giuseppe Saglio ◽  
Juan Luis Steegmann ◽  
Neil P. Shah ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myeloid Leukemia ◽  
Progression Free Survival ◽  
Early Response ◽  
First Line ◽  
Phase 3 ◽  
Free Survival ◽  
Key Points ◽  
Treatment Naïve

Key Points In a 3-year follow-up of the DASatinib versus Imatinib Study In treatment-Naive CML patients trial, first-line dasatinib resulted in faster and deeper responses compared with imatinib. Deeper responses at 3, 6, and 12 months were associated with better 3-year progression-free survival and overall survival.

scholarly journals Molecular profiling of advanced malignancies guides first-line N-of-1 treatments in the I-PREDICT treatment-naïve study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jason K. Sicklick ◽  
Shumei Kato ◽  
Ryosuke Okamura ◽  
Hitendra Patel ◽  
Mina Nikanjam ◽  
...  
Keyword(s):  
Disease Control ◽  
Progression Free Survival ◽  
Complete Response ◽  
Disease Control Rate ◽  
Unknown Primary ◽  
Combination Therapies ◽  
First Line ◽  
Free Survival ◽  
Treatment Naïve ◽  
Matching Score

Abstract Background Malignancies are molecularly complex and become more resistant with each line of therapy. We hypothesized that offering matched, individualized combination therapies to patients with treatment-naïve, advanced cancers would be feasible and efficacious. Patients with newly diagnosed unresectable/metastatic, poor-prognosis cancers were enrolled in a cross-institutional prospective study. Methods A total of 145 patients were included in the study. Genomic profiling (tissue and/or circulating tumor DNA) was performed in all patients, and PD-L1 immunohistochemistry, tumor mutational burden, and microsatellite status assessment were performed in a subset of patients. We evaluated safety and outcomes: disease-control rate (stable disease for ≥ 6 months or partial or complete response), progression-free survival (PFS), and overall survival (OS). Results Seventy-six of 145 patients (52%) were treated, most commonly for non-colorectal gastrointestinal cancers, carcinomas of unknown primary, and hepatobiliary malignancies (53% women; median age, 63 years). The median number of deleterious genomic alterations per patient was 5 (range, 0–15). Fifty-four treated patients (71%) received ≥ 1 molecularly matched therapy, demonstrating the feasibility of administering molecularly matched therapy. The Matching Score, which reflects the percentage of targeted alterations, correlated linearly with progression-free survival (R2 = 0.92; P = 0.01), and high (≥ 60%) Matching Score was an independent predictor of improved disease control rate [OR 3.31 (95% CI 1.01–10.83), P = 0.048], PFS [HR 0.55 (0.28–1.07), P = 0.08], and OS [HR 0.42 (0.21–0.85), P = 0.02]. Serious adverse event rates were similar in the unmatched and matched groups. Conclusions Personalized combination therapies targeting a majority of a patient’s molecular alterations have antitumor activity as first-line treatment. These findings underscore the feasibility and importance of using tailored N-of-1 combination therapies early in the course of lethal malignancies. Trial registration I-PREDICT (NCT02534675) was registered on August 25, 2015.

Overall survival (OS) of sorafenib (So) plus interleukin-2 (IL-2) versus So alone in patients with treatment-naive metastatic renal cell carcinoma (mRCC): Final update of the ROSORC trial.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 356-356
Author(s):  
Giuseppe Procopio ◽  
Elena Verzoni ◽  
Sergio Bracarda ◽  
Sergio Ricci ◽  
Laura Ridolfi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Ii ◽  
Single Agent ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Rank Test ◽  
Combination Regimen ◽  
First Line ◽  
Open Label ◽  
Treatment Naïve

356 Background: A randomized phase II trial evaluating So plus IL-2 versus So alone as first-line treatment of mRCC, did not show any difference in progression-free survival (PFS) (primary endpoint) between the two groups. The final overall survival analysis is here reported. Methods: In this open-label phase II study, 128 patients with mRCC were randomized to receive either oral So 400 mg bid continuous dosing plus IL-2 4.5 MIU subcutaneously administered 5 times weekly for 6 weeks every 8 weeks (Arm A), or So alone (Arm B). At relapse, most patients of the two arms underwent treatment with other targeted therapies (TTs) including sunitinib, everolimus, and axitinib. Overall survival was estimated by Kaplan-Meier method and compared by two-sided log-rank test. Results: According to Motzer criteria 55 % of the patients were low risk in both arms, and 41% and 39% were intermediate risk in Arm A and B respectively. After a median follow-up time of 58 months (interquartile range: 28-63 months), the median OS was 38 and 33 months in Arm A and B, respectively (p = 0.667). Five-year OS was 26.3% (95% CI: 15.9-43.5) for the combination arm and 23.1% (95% CI: 13.2-40.5) for single agent arm. The overall number of death was 85, 42 of whom in the So monotherapy group. Median PFS survival was 7.3 and 6.9 months for Arm A and B, respectively (p = 0.109). Overall, 49 (77%) and 48 (75%) patients in Arm A and B, respectively, received at least one subsequent targeted therapy (TTs). The most common adverse events (AEs) in both arms were asthenia, hand-foot syndrome, hypertension and diarrhoea. Grade 3-4 AEs were documented in 38% of patients treated with the combination regimen and in 25% of those undergoing single agent treatment. Conclusions: The OS results suggest an improved outcome in patients with mRCC treated with TTs which appears independent of the treatment initially administered. This prospective study, regarding use of sorafenib in first line of treatment, was associated with a surprising median OS. Clinical trial information: NCT00609401.

Efficacy of avelumab + axitinib (A + Ax) versus sunitinib (S) by IMDC risk group in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4574-4574
Author(s):  
John B. A. G. Haanen ◽  
James Larkin ◽  
Toni K. Choueiri ◽  
Laurence Albiges ◽  
Brian I. Rini ◽  
...  
Keyword(s):  
Risk Group ◽  
Objective Response ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Complete Response ◽  
Duration Of Response ◽  
Treatment Naïve ◽  
Group A ◽  
To Receive

4574 Background: In the phase 3 JAVELIN Renal 101 trial (NCT02684006), treatment-naive patients with aRCC receiving A + Ax showed improved progression-free survival (PFS) and objective response rate (ORR) across International Metastatic RCC Database Consortium (IMDC) risk groups (favorable [F], intermediate [I], and poor [P]) compared with patients receiving S. Here we report updated efficacy results for A + Ax vs S by IMDC risk groups from the third interim analysis. Methods: Patients were randomized 1:1 to receive either A (10 mg/kg intravenously every 2 weeks) plus Ax (5 mg orally twice daily) or S (50 mg orally once daily) for 4 weeks (6-week cycle). Patients were categorized per IMDC risk group into F, I, and P subgroups, and outcomes were assessed for F, I, P, and I + P. Overall survival (OS) and PFS, ORR, complete response (CR), and duration of response (DoR) per investigator assessment (RECIST v1.1) were assessed. Results: The study enrolled 886 patients with aRCC. At data cutoff (Apr 2020), median (95% CI) follow-up for OS in the A + Ax was NR (42.2-NE) vs 37.8 (31.4-NE) months with S. The Table shows OS, PFS, ORR, CR, and DOR by IMDC risk group. A + Ax generally showed improved efficacy compared with S across IMDC groups. Conclusions: Consistent with previously reported results from prior interim analyses, extended follow-up confirms the efficacy benefits of A + Ax vs S across IMDC risk groups in patients with aRCC. Patients continue to be followed up for the final OS analysis. Clinical trial information: NCT02684006. [Table: see text]

Capecitabine and oxaliplatin as first-line chemotherapy in patients with metastatic colorectal carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13578-13578
Author(s):  
C. Gennatas ◽  
V. Michalaki ◽  
S. Gennatas ◽  
A. Kondi-Paphiti ◽  
D. Voros ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Complete Response ◽  
First Line ◽  
Free Survival ◽  
Life Threatening ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
Unacceptable Toxicity ◽  
Line Chemotherapy

13578 Background: Capecitabine is an oral fluoropyrimidine with superior activity and safety compared with bolus 5-FU/LV in metastatic colorectal cancer (CRC). The aim of this study was to evaluate the efficacy and safety of a combination of capecitabine and oxaliplatin as first-line chemotherapy in patients with advanced CRC. Methods: Fourty-six patients (26 men and 20 women) with metastatic CRC entered this study. All patients were treated with capecitabine (1,000mg/m2 p.o.twice daily, days 1–14) and oxaliplatin (130mg/m2 on day 1). Cycles were repeated every 21 days until disease progression or unacceptable toxicity. Baseline characteristics: Median age 61 years (range 32–74), main sites of metastasis: Liver 32 patients (70%), liver and lungs 4 patients (9%), lungs 3 patients (6%), other sites 7 patients (15%). Results: 2 patients (4%) achieved complete response (CR), 17 patients (37%) achieved partial response (PR) and 7 patients (15%) attained stable disease (SD). With a median follow-up of 22 months the progression free survival was 7.5 months and overall survival was 19.0 months. All patients were assessable for toxicities. The most commonly encountered adverse events were from the gastrointestinal system (all grades 48%, grade 3, 6%). Neither toxic death nor life-threatening febrile neutropenia were reported. Conclusions: The combination of capecitabine and oxaliplatin is a convenient regimen in patients with advanced CRC that is associated with considerable efficacy and limited toxicity. No significant financial relationships to disclose.

First-line pembrolizumab (pembro) monotherapy in advanced clear cell renal cell carcinoma (ccRCC): Updated results for KEYNOTE-427 cohort A.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4570-4570 ◽  
Author(s):  
Scott S. Tykodi ◽  
Frede Donskov ◽  
Jae-Lyun Lee ◽  
Cezary Szczylik ◽  
Jahangeer Malik ◽  
...  
Keyword(s):  
Clear Cell ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Open Label ◽  
Cell Renal Cell Carcinoma ◽  
Duration Of Response ◽  
Prior Systemic Therapy

4570 Background: KEYNOTE-427 (NCT02853344) is an open-label, single-arm, phase 2 study to evaluate efficacy and safety of first-line single-agent pembro, a programmed death 1 (PD-1) inhibitor, in patients (pts) with ccRCC (cohort A) and non–clear cell RCC (cohort B). Updated follow up from cohort A are presented. Methods: Pts with histologically confirmed ccRCC, measurable per RECIST v1.1, and no prior systemic therapy were eligible. Pts received pembro 200 mg IV Q3W for 2 y or until confirmed progressive disease, unacceptable toxicity, or pt decision to withdraw. Primary end point was objective response rate (ORR; per RECIST v1.1 blinded independent central review). Additional end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: 110 pts enrolled; median (range) follow-up was 18.0 (2.5-22.7) mo. Median age (range) was 64 (29-87); 38.2%, 47.3%, and 14.5% had favorable, intermediate, and poor IMDC risk, respectively; 47.3% were PD-L1 positive. Confirmed ORR was 36.4% with 3 (2.7%) CRs and 37 (33.6%) PRs. Median DOR was not reached. Median PFS was 7.1 mo (95% CI, 5.6-11.0) and median OS was not reached. Results by IMDC category are outlined in the table. By PD-L1 status, confirmed ORR was 44.2% and 29.3% for positive and negative, respectively. By sarcomatoid differentiation (n=11), confirmed ORR was 63.6%. Treatment-related AEs occurred in 80.9%, with pruritus (28.2%) and fatigue (28.2%) most commonly reported. One pt died of treatment-related pneumonitis. Conclusions: With a median 18-months’ follow up, first-line pembro monotherapy continued to show antitumor activity in pts with ccRCC. Meaningful responses were observed in pts with intermediate/poor IMDC risk, PD-L1 positive and sarcomatoid differentiated tumors. Safety profile was comparable to previously reported. Clinical trial information: NCT02853344. [Table: see text]

ALPINE: Phase III zanubrutinib (BGB-3111) versus ibrutinib in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS7572-TPS7572 ◽  
Author(s):  
Peter Hillmen ◽  
Jennifer R. Brown ◽  
John C. Byrd ◽  
Barbara Eichhorst ◽  
Nicole Lamanna ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Complete Response ◽  
Geographic Region ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Open Label ◽  
Duration Of Response ◽  
Treatment Naïve ◽  
Independent Review ◽  
Ecog Ps

TPS7572 Background: Inhibition of Bruton tyrosine kinase (BTK) has emerged as a strategy for targeting B-cell malignancies including CLL/SLL. Zanubrutinib, an investigational inhibitor of BTK, was specifically engineered to optimize selectivity, half-life and solubility in an effort to decrease toxicities and better penetrate tumor tissue. Early clinical data suggested that zanubrutinib treatment in patients with treatment-naïve (TN; n = 16) or R/R (n = 50) CLL/SLL induced deep responses: 94% overall response rate (ORR), including 6% and 2% complete response rates in TN and R/R CLL/SLL, respectively (ICML 2017). This study is designed to evaluate whether zanubrutinib monotherapy exhibits non-inferior and potentially superior efficacy based on the ORR vs ibrutinib monotherapy in patients with R/R CLL/SLL. Methods: This ongoing phase 3, randomized, open-label, global study (NCT03734016, BGB-3111-305) is comparing the efficacy and safety of zanubrutinib vs ibrutinib in adult patients with R/R CLL/SLL. Approximately 400 patients will be randomized, 1:1 to each arm and stratified by age (< 65 vs ≥ 65 years), refractory status (yes vs no), geographic region, and del(17p)/ TP53 mutation status (present vs absent). Key inclusion criteria include R/R CLL/SLL requiring treatment per iwCLL criteria, ECOG PS 0-2, and adequate hematologic function. The primary endpoint is ORR as determined by an independent review committee according to iwCLL guidelines, with modification for treatment-related lymphocytosis for patients with CLL and per 2014 Lugano Classification for patients with SLL. The study is powered to test the non-inferiority and superiority of the ORR for zanubrutinib vs ibrutinib. Secondary endpoints include progression-free survival, safety, duration of response, and overall survival. Recruitment is ongoing. Clinical trial information: NCT03734016.

FRACTION-RCC: Innovative, high-throughput assessment of nivolumab + ipilimumab for treatment-refractory advanced renal cell carcinoma (aRCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5007-5007 ◽  
Author(s):  
Toni K. Choueiri ◽  
Harriet M. Kluger ◽  
Saby George ◽  
Scott S. Tykodi ◽  
Timothy M. Kuzel ◽  
...  
Keyword(s):  
Partial Response ◽  
Adaptive Design ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Duration Of Response

5007 Background: The immuno-oncology (I-O) combination nivolumab + ipilimumab (NIVO+IPI) is approved for first-line (1L) and NIVO is approved for second-line treatment post TKI therapy in aRCC. The open-label, randomized, phase 2 Fast Real-Time Assessment of Combination Therapies in Immuno-Oncology (FRACTION-RCC; NCT02996110) platform study has an adaptive design allowing rapid evaluation of I-O therapies, including NIVO+IPI or other investigational combinations. This FRACTION analysis reports preliminary outcomes with NIVO+IPI in aRCC pts after progression on checkpoint inhibitor therapy. Methods: All pts, except 1, had previously received and progressed on checkpoint inhibitor treatment. Pts received NIVO+IPI (NIVO 3 mg/kg + IPI 1 mg/kg Q3W ×4, then after 6 weeks, NIVO 480 mg Q4W), up to 2 years or until progression, toxicity, or protocol-specified discontinuation. Primary endpoints were confirmed objective response rate (ORR; per investigator using RECIST v1.1), duration of response (DOR), and progression-free survival probability at week 24. Safety outcomes were reported. Results: 46 pts were randomized to NIVO+IPI. Pts had 0 (n = 1), 1 (n = 10), 2 (n = 12), 3 (n = 10), or ≥4 (n = 13) prior lines of therapy. All pretreated pts had prior anti-PD-(L)1-, none had prior anti-CTLA-4- therapy, and 37 had prior TKI-based therapy; 45 pts progressed on anti-PD-(L)1 as the most recent therapy. Most pts had clear cell aRCC (n = 44). After a median study follow-up of 8.9 months, ORR was 15.2%; no pts achieved complete response and 7 achieved partial response. DOR ranged from 2–19+ months (n = 7); 5 pts had ongoing response. Six of 7 responders had received ≥2 prior lines of therapy. Any-grade treatment-related adverse events (AEs) were reported in 36 pts (78.3%; fatigue, rash [both 19.6%], and diarrhea [17.4%] were most common). Grade 3–4 treatment-related AEs were reported in 13 pts (28.3%; diarrhea [8.7%], ↑amylase and ↑lipase [both 6.5%] were most common). Treatment-related immune-mediated AEs of any grade were reported in 22 pts (47.8%; rash [19.6%], diarrhea [17.4%], and ↑alanine aminotransferase [8.7%]). No treatment-related deaths were reported. Updated and expanded results with an additional 3 months of follow-up will be presented. Conclusions: These results suggest that NIVO+IPI may provide durable partial response in some pts with prior progression on checkpoint inhibitors, including some heavily pretreated pts. The safety profile of NIVO+IPI in FRACTION pts was similar to historic data in aRCC with this combination. Clinical trial information: NCT02996110 .

scholarly journals Primary Clinical Response of Relmacabtagene Autoleucel in Adults with Relapsed/Refractory Follicular Lymphoma (r/r FL) in China

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2434-2434
Author(s):  
Yuqin Song ◽  
Zhitao Ying ◽  
Haiyan Yang ◽  
Ye Guo ◽  
Wenyu Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Duration ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
Free Survival ◽  
Duration Of Response

Abstract Background Most patients (pts) with r/r FL remain incurable and eventually relapse or progress. Previously, a Ph1 study of relma-cel (NCT03344367) had demonstrated preliminary safety and efficacy in r/r B-NHL pts, including those with r/r FL. A Ph2 pivotal study in r/r FL pts had been enrolled and preliminary efficacy, safety and PK was presented. Methods Adult pts were eligible with histologically confirmed grade (Gr)1-3a r/r FL on the basis of the 2016 WHO Classification, having failed ≥ 2-line prior therapies or relapsed after auto-HSCT, without allogeneic transplant within 90 days or primary central nervous system (CNS) lymphoma, and with ECOG performance score of 0-1. Pts were randomized to receive either 100×10 6 (low dose) or 150×10 6 (high dose) relma-cel (1:1) following fludarabine 25 mg/m 2 & cyclophosphamide 250 mg/m 2 daily×3. Pts were evaluated for efficacy (Cheson, 2014), toxicity (cytokine release syndrome [CRS] by Lee 2014, and others by CTCAE v4.03), and PK (by qPCR and flow cytometry). Primary endpoint was complete response rate (CRR). Secondary endpoints included objective response rate (ORR), frequency/severity of AEs, duration of response (DOR), duration of complete response (DoCR), duration of partial response (DoPR), time to primary remission (TTR), time to primary complete remission (TTCR), progression free survival (PFS), overall survival (OS), and CAR-T cell expansion. Disease response was by investigator assessment, a sensitivity analysis was also conducted using an independent review committee. Results Between June 2018 and June 2021, 28 r/r FL pts were enrolled and treated. As of the data cut-off of June 11, 2021, 20 pts were treated with relma-cel with ≥ 1 month of follow-up. Among these 20 pts, the median age was 54.5 years (range, 36-71), 50% of pts were male, 85% had ECOG 0, 10% had a sum of perpendicular diameters (SPD) ≥ 5000 mm 2, and 36% (5/14) had a FLIPI2 score≥ 3. Pts had received a median of 3.5 prior lines of therapy, 6 (30%) pts had received at least five lines of treatment and 65% were refractory to last prior treatment, 85% were relapsed, 50% were both relapsed and refractory. Relma-cel was successfully manufactured in all pts. Best ORR was 100% (19/19), and best CRR was 95% (18/19). For the mITT (n=19, one pt who developed gastric adenocarcinoma, was excluded, but also achieved CR), ORR at 1 month was 100%(19/19) and CRR was 63% (12/19). CRR at 3 months for 17 pts &gt; 3 months post treatment, was 82%(14/17). At a median follow-up of 8.9 months, the median duration of response [DOR], progression-free survival (PFS) and overall survival (OS) were not reached. Twenty pts who received relma-cel were evaluable for safety. Gr ≥3 AEs related to relma-cel occurred in 80% of pts, most commonly neutrophil count decreased (35%), lymphocyte count decreased (30%) and white blood cell count decreased (25%). CRS occurred in 35% (all Gr 1), and only 2 pts received tocilizumab. Median CRS onset was 7 days (range, 5-9), with median duration of 5 days. Two (10%) pts experience neurotoxicity (NT), both Gr 1, with onsets of 4 and 9 days, and duration of 25 and 7 days, respectively. No deaths occurred. Safety data, tocilizumab/steroids usage and PK parameters are shown in the Table. Conclusion With median follow-up of 8.9 months, relma-cel treatment in r/r FL pts had resulted in high tumor remission rates and a manageable toxicity profile in the first 20 pts treated. Data for additional patients will be presented. Table： The summary of AEs (AE, TEAE, CRS, NT), the usage of tocilizumab/steroids and PK Parameters Figure 1 Figure 1. Disclosures Yang: JW Therapeutics: Current Employment. Zhang: JW Therapeutics: Current Employment. Ma: JW Therapeutics: Current Employment. Zhou: JW Therapeutics: Current Employment. Zheng: JW Therapeutics: Current Employment.

Sign in / Sign up

Export Citation Format

Share Document