Phase II trial of radiation therapy/temozolomide followed by temozolomide/sorafenib in the first-line treatment of glioblastoma multiforme (GBM)

2018 Background: Anti-angiogenesis agents have recently shown activity in the treatment of patients (pts) with GBM. We added sorafenib, a multi-targeted TKI, to the standard first-line treatment of patients with GBM. Methods: Pts with histologically documented GBM were eligible at diagnosis or after resection. Additional entry criteria: ECOG PS 0 or 1; adequate organ function; ability to swallow pills; standard exclusions for antiangiogenesis agents. All pts initially received radiation therapy (total 60 Gy, 2 Gy by single daily fractions) plus temozolomide (75mg/m2 po daily). Four weeks after completion of radiation therapy, pts received temozolomide (150mg/m2 po days 1–5, repeated every 21 days for 6 cycles) plus sorafenib (400mg po bid daily x 24 weeks). Pts were evaluated every 8 weeks during temozolomide/sorafenib therapy, and every 3 months after therapy ended, until tumor progression. Median PFS was the primary endpoint. Results: Between April 2007 and July 2008, 45 pts were enrolled. The median age was 54 years; 30 pts (67%) had previous partial or complete surgical resection. 39 pts (87%) completed concurrent RT/temozolomide therapy, while 6 pts were removed from treatment (PD 4, toxicity 1, intercurrent event 1). 39 pts began treatment with temozolomide/sorafenib; 3 have completed all planned treatment, 8 remain on treatment, and 28 stopped treatment early (PD 22, toxicity 2, intercurrent event 1, pt decision 3). Best responses are as follows: CR, 1 pt (2%); PR, 5 pts (11%); stable disease, 22 pts (49%); progressive disease, 14 pts (31%). After a median follow-up of 9 months, median PFS for all pts was 6 months (95% confidence intervals, 2.7–7.8 months). Median PFS for pts who received at least 1 dose of sorafenib is also 6 months. The median overall survival is 16 months (95% CI, 7.2-NR months). Grade 3/4 toxicity during temozolomide/sorafenib was uncommon; 7 pts (16%) required dose reductions of sorafenib during their treatment course. Conclusions: The addition of sorafenib to standard treatment with RT/temozolomide is feasible and well tolerated by most pts. Preliminary efficacy is similar to standard therapy; updated results will be presented. [Table: see text]

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Bevacizumab (Bev), irinotecan (IRI), folinic acid (FA), and 5-fluorouracil (FU) every 2 weeks (BIFF regimen) as first-line treatment for metastatic colorectal cancer (MCRC) patients (pts): The SICOG experience

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15067 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15067-e15067

Author(s):

P. Comella ◽

B. Massidda ◽

D. Natale ◽

G. Filippelli ◽

A. Farris ◽

...

Keyword(s):

Primary Resection ◽

Hematologic Toxicity ◽

Severe Toxicity ◽

Line Treatment ◽

First Line ◽

Primary Colon ◽

Ecog Ps ◽

Age Range ◽

First Line Treatment

e15067 Background: The IRIFAFU regimen produced in MCRC pts a consistent activity (RR, 33% [95% CI, 27–39%], PFS, 7.4 [95% CI, 6.5–8.3] mo.) in 2 consecutive randomized SICOG trials . Bev was proven to significantly improve the efficacy of IFL regimen. Here we report the safety and activity results of the BIFF regimen as first-line treatment of MCRC. Patients: From Feb 2007 to Jul 2008, 95 pts with MCRC were treated: so far, 85 pts were evaluated for safety: M/F were 47/38, median age (range) was 64 (35–78) yrs. Fifty-six pts had a colon, and 29 pts a rectal carcinoma. ECOG PS was 0 (63 pts, 74%), or 1 (22 pts, 26%). Thirty-four (40%) pts had 1 site, 33 (39%) 2 sites, and 18 (21%) pts ≥3 sites of disease. Liver was involved in 66 (78%), lung in 23 (24%) pts. Twenty-one (25%) pts had an unresected primary (colon 13, rectum 8). Bev 5 mg/kg (1-h), and IRI 180 mg/sqm (1-h) were given IV on day 1, 6S-FA 250 mg/sqm (2-h), and FU 850 mg/sqm (bolus) were given IV on day 2 biweekly for a maximum of 12 cycles. Bev was continued until progression, severe toxicity, or refusal. Results: A median of 9 (range, 1–12) cycles of BIFF were delivered. G4 hematologic toxicity was: neutropenia (21%), and febrile neutropenia (10%). G≥3 non-hematologic toxicity was: diarrhea 15%, vomiting 7%, stomatitis 4%, hypertension 1%. No severe episodes of bleeding were registered. Among 81 assessable pts, 5 CRs (3 in liver, 1 in liver & nodes, 1 in liver & lung), and 41 PRs were registered, giving a RR of 57% (95% CI, 45–68%). Overall, 71/81 (88%, 95% CI, 77–93%) pts obtained a disease control. Liver mets resection, or primary resection, was safely performed in 3 pts and in 2 pts, respectively. After a median follow- up of 12 (range, 6–24) mo., median FFS was 8.4 (95% CI, 6.8–10.0), and median PFS was 14.1 (95% CI, 9.6–18.6) mo. With only 14 deaths, OS results are still immature. Conclusions: Unexpected side effects of the BIFF regimen were not registered. Addition of Bev increased the activity without worsening the tolerability of IRIFAFU combination as compared with our previous experience. Efficacy of BIFF was comparable with that reported with other Bev plus IRI-based combinations. Updated follow-up will be presented. No significant financial relationships to disclose.

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Phase I study of the IXO regimen, irinotecan (I), capecitabine (X), oxaliplatin (O), as first-line therapy for metastatic colorectal cancer: Final survival results

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4082 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4082-4082

Author(s):

J. Maroun ◽

D. Jonker ◽

C. Cripps ◽

R. Goel ◽

T. Asmis ◽

...

Keyword(s):

Colorectal Cancer ◽

Phase I ◽

Metastatic Colorectal Cancer ◽

Phase Ii ◽

Line Treatment ◽

First Line ◽

Common Grade ◽

Grade 3 ◽

Ecog Ps ◽

First Line Treatment

4082 Background: This study was designed to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and efficacy of the IXO regimen when used as first-line treatment for metastatic colorectal cancer (mCRC). Methods: Patients with ECOG PS 0–2, histologically proven, chemo-naïve, non-resectable mCRC were eligible. Phase I starting doses were as follows: I (180 mg/m2 i.v.) d1, X (850 mg/m2 bid orally) d2–15, O (85 mg/m2 i.v.) d1; q3w. Dose escalation (3+3 design) was based on toxicity observed at previous dose levels (DL) until DLT and the MTD were reached. Results: 39 pts (31 male/8 female, median age 58 years, ECOG PS 0–1 in 37, 95%) received a median of 11 cycles (range 1–34) at 8 DLs. 39 pts were evaluable for toxicity. The most common grade 3/4 hematological adverse events (AEs) were granulocytopenia (60%) and fever/febrile neutropenia (18%). The most common grade 3 non-hematological AEs were diarrhea (15%), vomiting (10%), fatigue (8%). No grade 3/4 neuropathy was reported. DLTs: 1 DLT was observed at each of the first 4 DLs, no DLTs at DL5 & 6, 1 at DL7 and 2 at DL8. MTD was reached at DL8. The recommended phase II dose (DL7) is as follows: I (160 mg/m2), X (950 mg/m2), O (100 mg/m2). Efficacy: 38 pts are evaluable for efficacy. The RR is 74% (95% CI 60–89), including 4 CRs, 25 PRs and 6 SDs. The disease control rate is 90% (95% CI 80–100). 10 (26%) pts had subsequent liver surgery with curative intent; 1 had lung resection. Median progression-free survival was 12.3 months (95% CI, 8–17). Overall median survival was 26.4 months (95% CI, 13–36). Conclusions: Diarrhea is the main DLT. Severe neutropenia was of short duration and manageable. The IXO regimen is well tolerated and highly effective as first-line treatment for mCRC. It appears to be particularly effective in downsizing of initially unresectable colorectal cancer liver metastases. A phase II study to confirm the efficacy/safety of IXO in combination with bevacizumab (Avastin) is ongoing. Supported by: Hoffmann La-Roche, Sanofi-Aventis, Pfizer Canada. [Table: see text]

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Phase IIb trial of fluorouracil, leucovorin, oxaliplatin, and paclitaxel (POF) compared with fluorouracil, feucovorin, and irinotecan (IF) as first-line treatment for advanced gastric cancer (AGC)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15642 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15642-e15642

Author(s):

R. Lin ◽

Q. Chen ◽

N. Fan ◽

Y. Ye ◽

Z. Guo ◽

...

Keyword(s):

Gastroesophageal Junction ◽

Complete Response ◽

Patient Choice ◽

Hematological Toxicity ◽

Line Treatment ◽

First Line ◽

Peripheral Neurotoxicity ◽

Grade 3 ◽

First Line Treatment

e15642 Background: Primary results of POF as 1st and 2nd line treatment for AGC have been presented at ASCO 2007 and 2008. We report here data on the feasibility and the toxicity of POF versus IF(Dank, et al, ASCO 2005) in 1st line treatment of AGC. Methods: Patients with previously untreated, advanced, unresectable, and histologically confirmed adenocarcinoma of the gastric or gastroesophageal junction were randomly assigned to POF or IF regiment. Treatment was continued until disease progressed, unacceptable toxicity, or patient choice. Results: 25 patients were entered in this study between March 2007 and July 2007: 13 in the POF group and 12 in the IF group. The median patient age was 55 years (range, 36 to 67 years), 18 were males and 7 were females. No complete response was observed. The response rate was 62.5% (POF) and 33.3% (IF) respectively. At a median follow-up of 285 days, 7(POF) versus 6(IF) patients were still alive. Hematological toxicity was the most frequent toxicity in both groups. Grade 3 to 4 neutropenia were 38.5% (POF) versus 8.3% (IF). Diarrhea was found 0% and 8.3% in POF and IF group respectively. No grade 3 peripheral neurotoxicity was observed. Conclusions: Compared with IF regiment, POF could also be used as first-line treatment for AGC with acceptable safety profile, good efficacy, and more encouraging results. No significant financial relationships to disclose.

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Liver resectability following mFOLFOX6 with bevacizumab as the first-line treatment of unresectable liver limited metastases from colorectal cancer in Japanese patients (KSCC 0802).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.666 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 666-666 ◽

Cited By ~ 1

Author(s):

Hironori Samura ◽

Toru Beppu ◽

Yasunori Emi ◽

Yoshihiro Kakeji ◽

Hiroshi Saeki ◽

...

Keyword(s):

Colorectal Cancer ◽

Japanese Patients ◽

Median Number ◽

Line Treatment ◽

First Line ◽

Eligibility Criteria ◽

Grade 3 ◽

Multi Center Study ◽

Ecog Ps ◽

First Line Treatment

666 Background: There is no data concerning liver resectability following mFOLFOX6 with bevacizumab as the first-line treatment of unresectable liver limited metastases from colorectal cancer by prospective, multi-center study in Japan. The Kyushu Study group of Clinical Cancer (KSCC) conducted a phase II trial in this setting. Methods: Eligibility criteria included unresectable liver limited metastases from histologically confirmed advanced colorectal cancer, ECOG PS 0-1 and adequate general condition. Patients (pts) received 6 cycles of mFOLFOX6 (oxaliplatin 85 mg/m2, l-leucovorin 200 mg/m2 d1 followed by 400 mg/m2 bolus 5-FU and a 46-hr 2,400 mg/m2 5-FU infusion every 2 weeks) with bevacizumab (5mg/kg) followed by evaluating the liver resectability. (UMIN000001308) Results: Of the 40 pts enrolled from Sept. 9 2008 to Aug. 10 2010; M/F, 29/11; Median age, 63 years (range 37-74); ECOG PS 0/1, 38/2. The median number of administration cycles was 6 (range, 1–7). Response for CR, PR, SD, PD and NE were 0 (0 %), 12 (30.0 %), 22 (55.0%), 3 (7.5%) and 3 (7.5%), respectively. An overall response rate was 30.0% (95% CI: 16.6 % – 46.5 %). The grade 3-4 adverse events were; leukopenia (10%), neutropenia (32.5%), febrile neutropenia (5%), fatigue (2.5%), appetite loss (2.5%), diarrhea (2.5%), mucositis (2.5%), high AST (2.5%) and ileus (2.5%). The number of cases to intent operation was 17 (42.5%), the liver resectability was 16/40 (40.0 %). The number of R0 cases was 10 pts (25.0%, 95% CI; 12.7 - 41.2 %). Conclusions: mFOLFOX6 with bevacizumab regimen is safe and effective for unresectable liver limited metastases from colorectal cancer, and might be to lead the high liver resectability.

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Phase II clinical trial of XELOX as first line treatment for patients with unresectable or metastatic gastric cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15062 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15062-15062

Author(s):

R. Xu ◽

B. Han ◽

Y. Shi ◽

J. Xiong ◽

Y. Li ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Objective Response ◽

Metastatic Gastric Cancer ◽

Line Treatment ◽

First Line ◽

Hand Foot Syndrome ◽

Grade 3 ◽

First Line Treatment

15062 Background: The survival of advanced gastric cancer remains poor, while no chemotherapy regimen was recognized standard. Oxaliplatin and Capecitabine (Xeloda) have demonstrated promising antitumor efficacy in advanced colorectal cancer. The present study was conducted to further evaluate the efficacy and safety of XELOX (Oxaliplatin and Xeloda) regimen in gastric cancer. Methods: Patients with unresectable or metastatic gastric cancer were enrolled into this study. They all receive the XELOX regimens (Oxaliplatin 130mg/ m2 intravenously in 2 hours on day 1 followed by oral capecitabine 1000mg/ m2 twice daily for 14 days every 3 weeks).We evaluated the response every 2 cycles. Results: The median age of the total enrolled 45 patients was 55 years (range, 22–82 years), including 32 male and 13 female. They received a median of 5 cycles (range, 2–8 cycles) of XELOX. 21 of 45 patients (46.7%) achieved an objective response, 1 patient (2.2%) had completed response. 17 patients (37.8%) experienced stable disease. Median time to tumor progression (TTP) and median overall survival were not available yet due to the further follow-up needed. Most toxicity events were mild to moderate in XELOX regimen, with grade 3/4 neutropenia of 8.9 %, thrombocytopenia of 6.7%, anemia of 11.1%, hand-foot syndrome of 6.7 % and diarrhea of 6.7 %. Grade 3 neuropathy was 4.4%. The patients with advanced gastric cancer had a good tolerance to this chemotherapy. Conclusions: XELOX is a highly effective first-line treatment for unrsectable and metastatic gastric cancer. The response rates in this trial seems to be similar to those observed with FU/leucovorin/oxaliplatin combinations. XELOX is tolerable well in the treatment of advanced gastric cancer. No significant financial relationships to disclose.

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Cetuximab plus 5-FU/FA/oxaliplatin (FOLFOX-4) versus FOLFOX-4 in the first-line treatment of metastatic colorectal cancer (mCRC): OPUS, a randomized phase II study

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4035 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4035-4035 ◽

Cited By ~ 34

Author(s):

C. Bokemeyer ◽

I. Bondarenko ◽

A. Makhson ◽

J. T. Hartmann ◽

J. Aparicio ◽

...

Keyword(s):

Adverse Events ◽

Performance Status ◽

Controlled Study ◽

Line Treatment ◽

First Line ◽

Ecog Performance Status ◽

Curative Intent ◽

Grade 3 ◽

Ecog Ps ◽

First Line Treatment

4035 Background: FOLFOX-4 is a standard first-line treatment for patients (pts) with mCRC. The IgG1 monoclonal antibody cetuximab has proven activity in combination with cytotoxic chemotherapy. Excellent response rates (RRs) have been reported with first-line cetuximab and FOLFOX-4. This randomized, controlled study was conducted to compare RRs of FOLFOX-4 + cetuximab vs FOLFOX-4. Methods: Pts with previously untreated epidermal growth factor receptor (EGFR)-expressing mCRC not resectable with curative intent were eligible. They were randomized 1:1, stratified by ECOG performance status (PS) (0–1 vs 2), to either Group A (cetuximab 400 mg/m2 initial dose then 250 mg/m2/week plus FOLFOX-4 every 2 weeks [oxaliplatin 85 mg/m2 day (d) 1; FA 200 mg/m2 d1, 2; 5-FU 400 mg/m2 bolus + 600 mg/m2 infusion over 22 h, d1, 2]) or Group B (FOLFOX-4 only). The primary objective was the best confirmed RR assessed by independent review; secondary objectives were progression- free survival (PFS), overall survival (OS), the R0 resection rate after metastatic surgery of curative intent and safety. Results: Between July 2005 and March 2006, 337 pts were randomized and treated in more than 70 centers in Europe. 181 (53.7%) pts were male; the median age of all pts was 61.0 years [24–82]; 305 (90.5%) pts had an ECOG PS of 0 or 1, and 32 (9.5%) of 2. The best overall confirmed RR was 45.6% in A and 35.7% in B. For pts with ECOG PS 0–1, RR was 49.0% in A and 36.8% in B (Odds Ratio 1.648, 95%CI [1.043- 2.604]). PFS and OS results are not yet available. The most common grade 3/4 adverse events were neutropenia (27.6% in A; 31.5% in B), diarrhea (7.1 and 6.0%), leucopenia (7.1 and 5.4%) and rash (9.4%, in A only). Conclusions: The addition of cetuximab increased the RR of FOLFOX-4 in first-line treatment of mCRC. Grade 3/4 adverse events, with the exception of skin rash, were not significantly more frequent in the cetuximab arm. No significant financial relationships to disclose.

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Rituximab Plus Short-Duration Chemotherapy As First-Line Treatment for Follicular Non-Hodgkin’s Lymphoma: A Phase II Trial of the Minnie Pearl Cancer Research Network

Journal of Clinical Oncology ◽

10.1200/jco.2005.05.004 ◽

2005 ◽

Vol 23 (7) ◽

pp. 1500-1506 ◽

Cited By ~ 34

Author(s):

John D. Hainsworth ◽

Sharlene Litchy ◽

Lisa H. Morrissey ◽

Michael B. Andrews ◽

Manuel Grimaldi ◽

...

Keyword(s):

Short Duration ◽

Phase Ii ◽

Phase Ii Trial ◽

Line Treatment ◽

First Line ◽

Short Course ◽

Short Course Chemotherapy ◽

Grade 3 ◽

First Line Treatment

Purpose To evaluate the feasibility and efficacy of rituximab with short-duration chemotherapy in the first-line treatment of patients with follicular non-Hodgkin’s lymphoma (NHL). Patients and Methods Patients with previously untreated stage II-IV follicular NHL, grade 1 or 2, were eligible for this multicenter phase II trial. All patients received four weekly doses of rituximab (375 mg/m2 intravenous), followed by three courses of combination chemotherapy (either cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], or cyclophosphamide, vincristine, and prednisone [CVP]) plus rituximab. Patients were evaluated for response after completing treatment, and were then followed up at 3-month intervals. Results Between January 2000 and July 2001, 86 patients were treated. Eight-two patients (95%) completed treatment; no patient was withdrawn due to toxicity. The overall response rate was 93%, with 55% complete responses. After a median follow-up of 42 months, the 3- and 4-year actuarial progression-free survivals were 71% and 62%, respectively. Five patients (6%) died from lymphoma; the overall actuarial survival at 3 years was 95%. Grade 3/4 leukopenia occurred in 53% of patients, but only six patients (7%) had neutropenia or fever. Grade 3/4 nonhematologic toxicities were uncommon. Conclusion Rituximab plus short-course chemotherapy is well tolerated as first-line treatment for patients with follicular NHL. The overall and complete response rates are similar to those reported with chemotherapy/rituximab combinations of longer duration. The actuarial progression-free survival of 62% at 4 years is encouraging, but further follow-up is necessary. Rituximab plus short-course chemotherapy may prove to be as effective as longer-duration chemotherapy and currently provides an attractive option for first-line treatment of elderly patients and others who tolerate chemotherapy poorly.

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Overview of the French Practice: Therapeutic Strategies in Patient's First Relapse or Refractory Non IgM AL Amyloidosis

Blood ◽

10.1182/blood-2018-99-114834 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3297-3297 ◽

Cited By ~ 1

Author(s):

Camille Villesuzanne ◽

Stephanie Harel ◽

Alexis Talbot ◽

Bruno Royer ◽

Naelle Lombion ◽

...

Keyword(s):

Overall Survival ◽

Partial Response ◽

Al Amyloidosis ◽

Line Treatment ◽

First Line ◽

Hematologic Response ◽

Organ Response ◽

Grade 3 ◽

First Line Treatment

Abstract First line treatment of systemic non IgM AL amyloidosis is well defined in the recommendations of the French National Reference Center for AL amyloidosis. Melphalan or cyclophosphamide at standard dose with dexamethasone in combination with bortezomib are currently recommended. The objective is to rapidly obtain an hematological response, modulating treatment according to severity of heart involvement and hematologic response. At relapse there are no such precise guidelines. If the initial treatment has been effective, it may be chosen in case of late relapse occurring after at least one year. Combination of other drugs effective in plasma cell dyscrasias might be proposed, but studies on treatment in the relapse setting are scarce and a consensus remains to be established. Here we report a multicenter retrospective study assessing treatment at relapse and evaluating their impact on hematologic response, progression-free survival (PFS), overall survival, organ responses and toxicity. We included 84 patients who received, from 2006 to 2014, as first line treatment, a non-intensive chemotherapy in 15 French hospital centers. At diagnosis, 47 (56 %), 51 (61%) and 16 (19%) patients respectively presented with heart, kidney, and neurological involvement. Twenty three patients (27%) had a severe heart disease with a Mayo Clinic stage III. The median follow-up of the cohort was 58 months (9-135). The hematological response was assessed at 3 months based on free light chain measurement, according to the international consensus. At relapse, 29 patients (34,5%) received a bortezomib, cyclophosphamide and dexamethasone combination (VCD) resulting in 79% of very good partial response (VGPR) or better and 7% of partial response (PR), 18 patients (21%) had an organ response, and with a median follow up of 70,5 months (9,03-135) the estimated overall survival at 3 years was 79,4%. Twenty six patients (31%) experienced grade ≥ 3 toxicities that were peripheral neuropathy in 5 patients. Seventeen patients (21%) received a combination of lenalidomide and dexamethasone (RD), resulting in 17% of VGPR or better and 35% of PR, 12 % of organ response with an estimated overall survival at 3 years of 94% with a median follow up of 46,5 months (20,99-122,97). Four patients (23%) had a grade ≥ 3 toxicity, mainly hematologic. Five patients (6%) received a combination of bortezomib with lenalidomide and dexamethasone (VRD) resulting in VGPR or better in 4 patients and PR in 1 patients, 4 patients had an organ response with all patients being alive at 3 years. Grade ≥ 3 toxicity was observed in 1 patient. Regarding these 3 combinations, the median PFS were respectively 22 months for VCD, 8 months for RD (p = 0, 0012) and 17.3 months for VRD. At relapse 13 other therapeutic combinations were used. Other IMIDs (thalidomide or pomalidomide), melphalan, bendamustine or daratumumab were given to 4, 8, 6 and 5 patients respectively resulting in 1, 4, 3 and 1 of VGPR or better hematologic response. Bendamustine containing regimens were associated in grade ≥ 3 toxicity in 5 patients (83%). Sixty-seven patients (79%) were still alive at 3 years. In conclusion, there is currently no consensus on the best treatment for AL amyloidosis patients in relapse. This study shows the different regimens used in France and their effectiveness in relapse. As usual in this disease the survival of relapsing patients is good with almost 80% of patients alive at 3 years. Bortezomib remains an important molecule in relapse. Lenalidomide alone with dexamethasone seems to be less effective to obtain a high rate of hematologic response. VRD has been used in few patients, we found no cumulative toxicity with the combination of proteasome inhibitor and lenalidomide with a very interesting response rate, PFS, OS and organ responses. VRD should be tested more systematically in relapsing or refractory patients. Finally, the role of daratumumab and new proteasome inhibitors remains to be defined. Disclosures Harel: janssen: Consultancy; takeda: Consultancy; amgen: Consultancy.

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Bendamustine, Bortezomib, and Rituximab in Patients with Previously Untreated Low Grade Lymphoma: A Phase II Trial of the Sarah Cannon Research Institute

Blood ◽

10.1182/blood.v120.21.1624.1624 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1624-1624 ◽

Cited By ~ 1

Author(s):

Ian W. Flinn ◽

Dana S. Thompson ◽

Ralph V. Boccia ◽

Gerald Miletello ◽

Andrew Lipman ◽

...

Keyword(s):

Cell Lymphoma ◽

Phase Iii ◽

Low Grade ◽

Line Treatment ◽

First Line ◽

Off Label ◽

Mantle Cell ◽

Grade 3 ◽

First Line Treatment

Abstract Abstract 1624 Background: Rituximab and bendamustine combination regimens have demonstrated high activity in non-Hodgkin's lymphoma (NHL). A phase III trial compared bendamustine plus R-CHOP as first-line treatment for follicular, indolent, and mantle cell lymphoma (Rummel ASH 2009). Bendamustine plus rituximab had an overall response rate of 94% and a complete remission rate of 40% compared to 94% and 31%, respectively, for R-CHOP. Phase III trials evaluating bendamustine plus rituximab as first-line therapy for patients (pts) with indolent and mantle cell lymphoma have shown equivalent or superior results when compared to R-CHOP or R-CVP as first-line treatment for indolent lymphoma. Bortezomib is a small molecule proteasome inhibitor that has shown substantial activity in multiple myeloma and lymphoma. Pre-clinical studies demonstrate significant synergy and/or ability to overcome resistance to a variety of current and investigational treatments for lymphoma. This trial evaluated the activity of bendamustine, bortezomib, and rituximab (BBR) in patients with previously untreated low-grade lymphoma. Methods: Eligible patients had histologically-confirmed follicular center cell (FCC) lymphoma (grade 1 or 2), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), or lymphoplasmacytic lymphoma (LPL); lymph node biopsy containing CD20+ B-cells; Ann-Arbor Stage 2, 3, or 4 disease; no previous systemic treatment for lymphoma; bi-dimensional measurable disease with at least 1 lesion measuring > 2.0 cm in a single dimension; ECOG PS 0–2. Treatment for all patients was given in 28-day cycles for a maximum of 6 cycles. Patients received rituximab 375 mg/m2 IV on days 1, 8, and 15 of cycle 1 (cycles 2–6, rituximab only on day 1); bendamustine 90 mg/m2 IV on days 1 and 2; and bortezomib 1.6 mg/m2IV on days 1, 8, and 15. Response evaluations were performed after cycle 3 and cycle 6. Patients were permitted to begin maintenance treatment with rituximab 6 months after completion of study treatment and after 6-month follow-up assessments have been conducted. Results: Between 1/2010 and 11/2011, 55 patients were enrolled with a median age of 62 years (range 30–89). Fifty one percent were male, 85% stage III or IV. Diagnoses were: FCC, 38pts (69%); MZL, 8pts (15%); SLL, 5pts (9%) and LPL, 4pts (7%). The median follow-up is 13 months (range: 6–26). At the time of this analysis, 78% of pts had completed 6 cycles of BRR, and 56% had continued to maintenance rituximab. Two pts remain in the first 6 cycles of BRR. Five pts (9%) discontinued treatment due to toxicity (1pt G2 neuropathy, 1 pt G2 atrial fibrillation, 1 pt G3 pancreatitis, 1 pt G3 diarrhea, 1pt G2 rash). The remaining 5 pts discontinued prematurely (1pt death due to stroke, 1pt wound complication, 1 pt lost to follow-up, 2 pts off due to request). Objective response was achieved in 89% of pts; 26pts (47%) complete response, 23pts (42%) partial response, 2pts (4%) stable disease, and 4pts (7%) unevaluable at the time of this analysis. Related grade 3/4 hematologic toxicities were: neutropenia (25%), febrile neutropenia (2%), thrombocytopenia (5%), and anemia (4%). We observed no grade 4 treatment related non -hematologic adverse events, the most common grade 3 were neuropathy (9%), diarrhea (7%), fatigue (7%), constipation (5%), and rash (5%). Time-to-event data are immature and will be the subject of a later analysis. At the time of data cut-off, 3 pts (5.5%) had progressed or relapsed and 3pts (5.5%) had died. Conclusion: BBR was well tolerated and produced high CR and OR rates. Toxicities including neuropathy were modest. Further study of this regimen in patients with previously untreated lymphoma is warranted. Disclosures: Off Label Use: Off-label bendamustine and bortezomib in first-line treatment for lymphoma. Boccia:Cephalon: Research Funding.

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