90Yttrium-Ibritumomab-Tiuxetan as First-Line Treatment for Follicular Lymphoma: 30 Months of Follow-Up Data From an International Multicenter Phase II Clinical Trial

2013 ◽  
Vol 31 (3) ◽  
pp. 308-313 ◽  
Author(s):  
Christian W. Scholz ◽  
Antonello Pinto ◽  
Werner Linkesch ◽  
Ola Lindén ◽  
Andreas Viardot ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
Residual Disease ◽  
Standard Procedure ◽  
Complete Response ◽  
Molecular Response ◽  
First Line ◽  
Ibritumomab Tiuxetan ◽  
Multicenter Phase

Purpose We report on a multicenter phase II trial of 90yttrium-ibritumomab-tiuxetan (90YIT) as first-line stand-alone therapy for patients with follicular lymphoma (FL). Patients and Methods Fifty-nine patients with CD20+ FL grade 1 to 3a in stages II, III, or IV, age 50 years old or older requiring therapy were enrolled. They received 90YIT according to standard procedure. If complete response (CR) or unconfirmed complete response (CRu) without evidence for minimal residual disease (MRD) 6 months after application of 90YIT was achieved, patients were observed without further intervention. The same applied to patients with partial response (PR) or with stable disease (SD). Patients with CR but with persisting MRD were to receive a consolidation treatment with rituximab. Primary end point was the clinical and molecular response rate. Secondary end points were time to progression, safety, and tolerability. Results Six months after treatment with 90YIT, 56% of the patients showed a CR or CRu and 31% achieved a PR. After a median follow-up of 30.6 months, the progression-free survival (PFS) was 26 months. There was a trend for shorter PFS in patients with increased lactate dehydrogenase (LDH). Of the 26 patients who had CR 12 months after 90YIT, only three had relapsed. Median time to next treatment has not been reached. The most common toxicities were transient thrombocytopenia and leukocytopenia. Nonhematologic toxicities never exceeded grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE v2.0). Conclusion 90YIT is well tolerated and achieves high response rates. Patients with increased LDH tend to relapse earlier, and individuals in remission 1 year after 90YIT appear to have long- lasting responses.

scholarly journals 90Y-Ibritumomab-Tiuxetan Consolidation in First-Line Complete Response Follicular Lymphoma Patients. Single Center Outcomes Analysis after Five Years Median Follow-up

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5323-5323
Author(s):  
Marcio Andrade-Campos ◽  
Natalia Espinosa-Lara ◽  
Paola Lievano ◽  
Luis Lopez-Gomez ◽  
Teresa Baringo ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Complete Response ◽  
Consolidation Therapy ◽  
First Line ◽  
Ibritumomab Tiuxetan ◽  
First Line Therapy ◽  
Line Therapy ◽  
The Mean ◽  
Line Of Therapy

Abstract Introduction: Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma accounting for around 22% of them. Their natural history is characterized by multiple relapses and progressively shorter response durations after every new line of therapy for this is desirable to offer the best first-line approach to each patient. However, still now this aspect remains unclear. In the current guidelines several first line options are included: immunotherapy (Rituximab (R) x4 or Lenalidomide+/- R), immunochemotherapy (CHOP, RCVP, Bendamustine + R), radioimmunotherapy for elderly patients. Moving forward, the consolidation with radioimmunotherapy or extended dose immunotherapy (R every 8 weeks for 4 or 12 doses) still appears as an optional part of the therapy (NCCN V3.2016). Radioimmunotherapy with 90Yttrium-ibritumomab tiuxetan (90Y-IT) is available in our institution since 2006 and more than 100 patients have been treated with RIT since then. Here an institutional analysis focus in their use as consolidation is presented. Aim: To analyze the experience with 90Y-IT as a consolidation therapy in patients in CR after first-line therapy. Patients & methods: A retrospective analysis was performed including all the patients that have received RIT with 90Y-IT. Inclusion criteria were: patients 18 years or older with a grade 1-2a follicular lymphoma, RIT was received as a consolidation therapy in complete response (CR) after a first-line therapy. Demographic and follow-up data were included. International working group (IWG) criteria of response was used. Progression free survival (PFS) was calculated from the date of RIT to the date of a confirmed relapse according IWG criteria, overall survival (OS) was calculated from the FL diagnosis to the last contact. Results: A total of 31 FL patients have received 90Y-IT been in CR after a first-line of therapy and were included for the study. Mean age at diagnosis was 61.2 (29-86) years with a female predominance (19, 61.3% vs. 12, 38.7%). 80.6% (26) with ECOG 0-1 and 19.4 ECOG 2. A third of them (10, 32.3%) were diagnosed with low tumor burden (stage I-II), 2 (9.7) of them presented extra nodal infiltration (subcutaneous and gut) and 12 (38.7%) showed bone marrow infiltration demonstrated by flow cytometer or biopsy. There were no patients with bulky disease. Stages: I: 7 (22.6%), II: 3 (9.7%), III: 9 (29.1%), IV: 12 (38.7%). As first-line therapy the patients received: Rx4: 11 (35.5%) cases, R-Cyclophosphamide vincristine prednisone (R-COPx6): 3 (9.7%) cases and 17 (54.8) R-cyclophosphamide doxorubicin, vincristine and prednisone (R-CHOP21x4-6). The median follow-up was 58.0 (10-107) months. During this time only 5 (16.1%) of patients have relapsed and need another therapy. None of the patients that have received R-CHOP+90Y-IT have relapsed; the relapsed patients received Rx4 (4) and R-COP (1). The median PFS after 90Y-IT has not reached, the mean was 83.3 (71.7-94.98) months, see Fig 1. Four (12.9%) patients have died, none of them were relapsed and the mortality was due to other causes. The median OS was not reached, the mean was 95.8 (85.6-106.1) months. As long-term events one 82 years old patient developed a colon cancer after 67 months of RIT, one 72 years old female a breast cancer after 17 months of RIT and one 71 years patients a MGUS after 24 months of RIT, none of them related with mortality events. Conclusions: The use of immunotherapy with rituximab or combined schedules with immunochemotherapy (R-COP and R-CHOP) followed by consolidation with 90Y-IT remains as a valid option for follicular lymphoma patients. After ~5 years of follow-up: 63.6% (Rx4+RIT), 66.7% (R-COP+RIT) and 100% (R-CHOP+RIT) of patients continue with complete response and off of therapy. Disclosures No relevant conflicts of interest to declare.

Fluctuating Values of Molecular Residual Disease (MRD) without Molecular Progression After Imatinib Discontinuation in Patients (pts) with Chronic Myeloid Leukemia (CML) Who Have Maintained Complete Molecular Response: Implications for Re-Treatment Criteria and Role of Prior Interferon Therapy. A Pilot Study of the French CML Group (FILMC),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3781-3781 ◽  
Author(s):  
Philippe Rousselot ◽  
Pascale Cony Makhoul ◽  
Delphine Rea ◽  
Philippe Agape ◽  
Franck E Nicolini ◽  
...  
Keyword(s):  
Interferon Therapy ◽  
Residual Disease ◽  
Imatinib Therapy ◽  
Molecular Response ◽  
Relapse Free Survival ◽  
First Line ◽  
Free Survival ◽  
Low Levels ◽  
Sokal Score

Abstract Abstract 3781 Background. We have reported the results of imatinib discontinuation in CML pts in complete molecular response (CMR) for more than 2 years under imatinib therapy (STIM study, Mahon et al. Lancet Oncol. 2010). Among the group of pts without confirmed molecular relapse, a small proportion exhibited low levels of detectable residual disease during a prolonged period of time. Aims. In order to better characterize this phenomenon, we decided to analyse pts who stopped IM following a maintained CMR or an undetectable molecular residual disease (UMRD) and resumed therapy upon loss of major molecular response (MMR). We also aimed to validate the loss of MMR as a robust criterion for the re-introduction of tyrosine kinase inhibitors (TKIs). Patients and methods. CP-CML pts were eligible if they were in CMR (CMR4.5: BCR-ABL/ABL IS ratio <0.0032%) or UMRD (undetectable Bcr-Abl using standardized RTQ-PCR) under imatinib therapy for more than 2 years. Those pts were not enrolled in the STIM study because the study was closed or because they experienced at least one positive value of the BCR-ABL/ABL ratio during the 2 years follow-up. The proposed criterion for resuming imatinib was the loss of MMR (BCR-ABL/ABL IS ratio >0.1%). We calculated relapse free survival (RFS) using three different end-points: First loss CMR/UMRD defined by one occurrence MRD positivity; second loss of CMR/UMRD using the STIM definition (two consecutive increasing values of MRD); third loss of MMR. We also described pts with long lasting fluctuating PCR values. Results. 34 CP-CML pts were included in the analysis. Median follow-up after imatinib discontinuation was 21.3 months (2.2–83.1). Sex ratio (M/F) was 50% with a median age of 54.1 years (27.4–78.2). Sokal score distribution was 34.5%, 37.9% and 27.6% for low, intermediate and high values respectively. 19 out of 34 (55.9%) of the pts received interferon therapy prior to imatinib. Median duration of imatinib therapy and median duration of CMR/UMRD prior to discontinuation was 63.8 months (30.1–120.8) and 33.7 months (7.3–72.8) respectively (only two pts had CMR/UMRD duration less than 2 years). Of note 18 out of 34 pts (52.9%) had a least one MRD positive value after the achievement of CMR/UMRD. After imatinib discontinuation, we identified 11 pts (32.4%) who experienced repeated low levels of detectable MRD without losing their MMR. Median follow-up for these pts with fluctuating values of MRD was 15.4 months (3.5–59.5) and none of them restarted imatinib. We next analysed relapse free survival (RFS) using the loss of MMR criteria (RFS-MMR). Median RFS-MMR was not reached, compared to median RFS using the loss of CMR/UMRD criteria (4.8 months) and median RFS using the STIM criteria (13.8 months) (p=0.003). As a consequence, 62.8% of the pts remain treatment free at 2 years using the loss of MMR criteria for resuming imatinib. Fluctuating values of MRD has already been described after interferon cessation in CML interferon treated pts. We thus asked if prior therapy with interferon before imatinib may influence treatment free survival. Duration of imatinib therapy and Sokal score risk distribution were comparable between pre-treated and non pre-treated pts (p=0.7). However, the median RFS was longer in interferon pre-treated pts as compared to pts who received imatinib first line (not reached versus 7 months, p=0.047). Furthermore, this difference was not significant using the loss of CMR/URMD (p=0.27) to define molecular relapse. Conclusions. We were able to identify a significant number of pts with fluctuating values of MRD after imatinib discontinuation, a proportion underestimated in previous studies. We also validated the loss of MMR as the most accurate and robust criteria for restarting imatinib after imatinib discontinuation. Applying this criterion, we demonstrated that treatment free survival is significantly better in pts previously treated with interferon before imatinib compared to pts who received imatinib as first line therapy. An update of this pilot study on a larger number of patients will be presented. Disclosures: Rousselot: BMS, Novartis: Research Funding. Tulliez:Novartis:. Mahon:Novartis Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria; Pfizzer: Honoraria.

90Yttrium-Ibritumomab Tiuxetan as First Line Treatment for Follicular Non-Hodgkin Lymphoma. 5 Year Results from an International Multicenter Phase II Clinical Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1806-1806 ◽  
Author(s):  
Kristina Lerch ◽  
Corinna Leng ◽  
Antonello Pinto ◽  
Werner Linkesch ◽  
Heinz Sill ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Remission Rate ◽  
Transformation Rate ◽  
Secondary Malignancies ◽  
First Line ◽  
Ibritumomab Tiuxetan ◽  
Advisory Committees ◽  
Bulky Disease ◽  
Multicenter Phase

Abstract Purpose Updated 5 year results are presented from the multicenter phase II trial of 90Yttrium-Ibritumomab-Tiuxetan (90YIT) as first line stand-alone therapy for patients with follicular lymphoma (FL). Patients and Methods 59 patients with CD20-positive FL grade 1 to 3a in stages II with bulky disease (n=12), III (n= 26), or IV (n=21), and in need for therapy, were enrolled between 05/2007 and 06/2010. They received 90YIT according to standard procedure (rituximab 250 mg/m2 days -7 and 0, then 90YIT 15 MBq/kg (0.4mCi/kg) day 0; patients with platelet counts below 150.000/ul but above 100.000/ul received only 11 MBq/kg). Primary end point was the clinical and molecular remission rate. Secondary end points were time to progression, safety, and tolerability. Results at 5 years after therapy with 90YIT are presented. Results Clinical remission rate (CR, Cru) 6 months after treatment with 90YIT was 56% (33 patients), while 31% had achieved a PR (18 patients). Median follow-up was 5 years with 8 patients lost to follow-up. Progression free survival was 2.6 years. Of the 26 patients who were in CR 12 months after 90YIT 57% were still without progress after 5 years, PFS after 90YIT was not reached versus 1.13 years for patients without CR 12 months after treatment (P =0.025, HR 2.474). Elevated LDH predicted a shorter PFS (4.0 years vs. 1.3 years, P=0.056). Some of the patients had extensive disease at time of treatment. Ann Arbor stadium did not differ significantly in response rate and 5 year PFS (II with bulky disease 50%, III 42.3%, IV 33.3%, P=0.12). Median time to next treatment (TTNT) for the whole population was 3.95 years (5-year TTNT-free, 50%). 5 year overall survival since treatment with 90YIT was 80%. Cause of Death was progressive disease (1 patient), secondary malignancy (3 patients) and others (6 patients). As previously reported, most common toxicities were transient thrombo- and leukocytopenia. Non-hematologic toxicities never exceeded grade II (CTCAEv2.0). No unexpected toxicities emerged during 5 year follow-up. Secondary malignancies occurred in 5 patients within 5 years after treatment with 90YIT (8%, oropharyngeal cancer, pancreatic cancer, lung carcinoma, cerebellar tumor, adenocarcinoma of the colon). All these cases had occurred shortly after therapy, suggesting pre-existing morbidity (retrospectively confirmed in 2 cases) or chance association (3 cases). Cases of acute myeloid leukemia were not reported. Transformation occurred in 8 patients (14%) with an annual transformation rate of 2.7%. Conclusion 90YIT is well tolerated and achieves a 5 year PFS of 40%. Considering that this treatment is a very short procedure (two outpatient drug applications one week apart) this appears remarkable. While patients with elevated LDH tend to relapse early, individuals who continue to be in CR 1 year after 90YIT achieve significantly long responses with a 5 year PFS of 59%. Secondary malignancies and transformation rate were not elevated after 5 years of follow up. 90YIT can be considered for the initial treatment of FL in patients who are unable or unwilling to tolerate standard therapy. Disclosures Pinto: Takeda, Roche, Celgene, Servier, Janssen, Helssin: Honoraria. Viardot:Takeda: Other: travel support; Roche: Honoraria; Pfizer: Honoraria; BMS: Consultancy; Janssen: Consultancy; Amgen: Consultancy. Keller:Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Spectrum Pharmaceutical: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hess:Janssen: Honoraria; Roche, CTI, Pfizer, Celgene: Research Funding; Pfizer: Honoraria; Roche: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Scholz:Spectrum Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Pezzutto:Cellgene, Novartis, Roche, Gilead: Membership on an entity's Board of Directors or advisory committees.

Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) Induces Long-Term Responses in Patients with Relapsed or Refractory Follicular Lymphoma (FL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2629-2629
Author(s):  
Russell J. Schilder ◽  
Thomas E. Witzig ◽  
Ian Flinn ◽  
Leo I. Gordon ◽  
Christos Emmanouilides ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Complete Response ◽  
Low Grade ◽  
Ibritumomab Tiuxetan ◽  
Bulky Disease ◽  
Prior Therapy ◽  
Yttrium 90

Abstract Background: Radioimmunotherapy (RIT) is an emerging clinical treatment option for patients with non-Hodgkin’s lymphoma (NHL). Yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin®) RIT was approved by the FDA in February 2002 for the treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell NHL, including patients with rituximab-refractory follicular NHL. In 4 registrational trials of 90Y ibritumomab tiuxetan conducted between 1996 and 1999, 211 patients with B-cell NHL were treated. Of these 211 patients, 153 patients (73%) had follicular lymphoma (FL). With ongoing follow-up, long-term durable responses have been observed, but until now have not been more fully characterized. Methods: Responding patients with time to progression (TTP) of ≥12 months were identified and characterized as long-term responding (LTR) patients. Results: In the 4 registrational trials, 78 of the 211 patients (37%) were identified as LTR patients. Characteristics of these LTR patients were as follows: median age 58 years (range, 24 to 80), 44% >60 years old, 55% male, 76% with follicular lymphoma, and 41% with lymphomatous marrow involvement. LTR patients had a median of 2 prior regimens (range, 1–9): 59% had ≥2 prior therapies, 33% had ≥3 prior therapies, and 37% had no response to their last prior therapy. Thirty percent of LTR patients had bulky disease (tumor size >5 cm) and 83% had stage III/IV disease. At the time of this analysis, the median duration of response (DR) and TTP for LTR patients were 28 months (range 11–80) and 29 months (range 12–82), respectively, with a median follow-up of 50 months (range 13–82). The median DR to the last prior therapy for LTR patients was 12 months. The complete response rate (confirmed [CR] and unconfirmed [CRu]) among LTR patients was 65%, and the median DR and TTP were 29 and 31 months, respectively, for CR/CRu patients. In ongoing responders the median DR is 52 months (range 48–80). Among the 153 patients with FL, 59 (39%) were identified as LTR patients. Compared to the overall LTR patients, LTR patients with FL had similar disease characteristics, DR, TTP, and CR/CRu rates. Conclusions: Ongoing follow-up indicates that 90Y ibritumomab tiuxetan frequently produces durable long-term responses (TTP ≥12 months) in patients with relapsed or refractory B-cell NHL. Failure to respond to the therapy immediately prior to treatment with 90Y ibritumomab tiuxetan does not appear to affect the ability to achieve long-term responses with 90Y ibritumomab tiuxetan. Durable long-term responses were achieved in 37% of all patients and 39% of patients with FL treated in 4 registrational trials of 90Y ibritumomab tiuxetan at 30 centers in the US. Of these LTR patients, a high proportion were >60 years old and had received ≥3 prior therapies.

Bendamustine Is Highly Effective for Relapsed or Refractory Indolent B-Cell Non-Hodgkin Lymphoma (B-NHL) and Mantle Cell Lymphoma (MCL): Final Results of a Japanese Multicenter Phase II Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3694-3694 ◽  
Author(s):  
Michinori Ogura ◽  
Toshiki Uchida ◽  
Kiyoshi Ando ◽  
Ken Ohmachi ◽  
Kuniaki Itoh ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Multicenter Phase ◽  
Number Of Patients ◽  
Highly Effective ◽  
Grade 3

Abstract Abstract 3694 Poster Board III-630 [Background and Purpose] Bendamustine hydrochloride is a bifunctional alkylating agent with novel mechanisms of action. Although bendamustine is known to have anti-tumor activity against indolent B-NHL as a single agent, efficacy in MCL with bendamustine monotherapy has not been reported. To assess the efficacy and toxicity of bendamustine in patients with relapsed indolent B-NHL and MCL, we conducted a multicenter phase II study. [Patients and Methods] Patients diagnosed with relapsed or refractory indolent B-NHL or MCL, 75= or >age= or >20, and PS 0-1 (ECOG) were enrolled in the study. Bendamustine was administered intravenously at a dose of 120 mg/m2 infused over 60 minutes on days 1 and 2 of each 21-day treatment cycle for up to 6 cycles (minimum of 3 cycles). The primary endpoint was the overall response rate (ORR). Tumor response was assessed by a central radiological review committee according to the International Workshop Criteria for NHL (1999). [Results] A total of 69 patients were enrolled and treated, including 52 (75%) cases of follicular lymphoma (FL) and 11 (16%) cases of MCL, ages 33 to 75 years, with predominantly stage III/IV indolent B-NHL (86%) or MCL (64%). The median number of unique prior therapies was two (range, 1 to 16), and sixty-six patients (96%) had received rituximab as a prior therapy. Twenty-nine patients (42%) completed the planned six cycles of chemotherapy, with fifty patients (72%) receiving 3 or more cycles. Dose reduction of bendamustine was required in 11 patients (16%). The ORR was 91% (63 of 69 patients; 95% CI, 82% to 97%) with a complete response (CR) rate of 67% (%CR), including %CRu (46 of 69 patients; 95% CI, 54% to 78%). The ORR in FL and MCL was 90% and 100%, respectively. The %CR in FL and MCL was 66% and 73%, respectively. Median progression-free survival (PFS) for all 69 patients was not reached at the median follow-up duration of 248 days (39-359 days). Median PFS for indolent B-NHL (58) and MCL (11) patients was not reached at the median follow-up duration of 254 days and 226 days, respectively. Hematologic toxicities, including grade 4 lymphopenia (72%) and neutropenia (48%), were the most frequently reported toxicities in patients. Non-hematologic toxicities were mild, with no grade 4 non-hematologic toxicity recorded. The most frequently reported grade 3 non-hematologic toxicities were GI toxicities (9%) including grade 3 vomiting (4%) and anorexia (3%), and infections (7%) which included one case of grade 3 febrile neutropenia, pneumonia, herpes infection, and viral pharyngitis. [Conclusion] Bendamustine monotherapy is a highly effective and less toxic treatment in patients with relapsed or refractory indolent B-NHL and MCL who have been pretreated (96%) with rituximab. It is noteworthy that a very high complete response rate (73%) was achieved in relapsed or refractory MCL patients although the number of patients was relatively small. Disclosures: No relevant conflicts of interest to declare.

Nilotinib Or High-Dose Imatinib Compared With Standard-Dose Imatinib In Early Chronic Phase CML Patients Who Have Suboptimal Molecular Responses To Standard-Dose Imatinib: Including Updated Data From RE-Nice Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1499-1499
Author(s):  
Soo-Young Choi ◽  
Sung-Eun Lee ◽  
Yun Jeong Oh ◽  
Soo-Hyun Kim ◽  
Richard C. Woodman ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Advanced Disease ◽  
Residual Disease ◽  
Standard Dose ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
High Dose ◽  
Molecular Response ◽  
First Line

Abstract Background In chronic myeloid leukemia (CML), achievement of optimal responses by time point has improved long-term outcomes. In IRIS study, patients who achieved major molecular response (MMR) at 18 months had event-free survival (EFS) benefit, compared to those who achieved complete cytogenetic response (CCyR) without MMR. However, the best treatment for these patients is still not confirmed. By the previous studies, sustaining standard-dose of imatinib (IM) is expected to yield less than 20 percent of additive MMR. In this study, we investigated the efficacy of switching to nilotinib (NIL) versus high-dose IM versus standard-dose IM for patients with suboptimal molecular response to IM as first-line therapy. Methods Early chronic phase (CP) CML patients who have achieved CCyR but no MMR after at least 18 months and up to 24 months ( 18 to 24 months) on first-line IM therapy at a daily dose of 400 mg were enrolled in RE-NICE study, and informed consents were obtained from all patients. In NIL arm, patients received 400 mg BID (800 mg/day) and in high-dose IM arm, patients received 800 mg/day administrated as 400 mg BID. Primary endpoint is to evaluate the cumulative MMR rates by 12 months, and secondary endpoints are to evaluate the cumulative MMR, MR4.0 and undetectable molecular residual disease (UMRD) rates during further 24 month follow-up. The efficacy of switching to NIL or high-dose IM were compared with that of the patients who maintained standard-dose of IM. Patients with standard-dose IM were selected with the same inclusion criteria and maintained standard-dose IM after enrollment period. To compare the efficacy among three groups, MMR rate, MR4.0 and undetectable molecular residual disease (UMRD) rates by 12 months were analyzed. Safety profiles also be assessed. Patients showing lack of response (lack of complete hematologic response (CHR) at 6 months, increasing WBC, no major cytogenetic response (MCyR) at 24 months), loss of response (loss of CHR or MCyR) or severe intolerance to treatment were allowed to crossover to the alternative treatment. Results With a data cut-off date of 15 Jul 2013, a total of 52 patients were randomized into NIL arm (n = 26) or high-dose IM arm (n = 26) and 16 patients were included in standard-dose IM group. With a median follow-up of 21 months (range, 1-36) in NIL arm and high-dose IM arm, all patients have maintained CCyR without progression to advanced disease, and progressive decrease in BCR-ABL1 transcript levels was observed in all patients. With a median follow-up of 12 months (range, 1-60), all patients in standard-dose IM group have maintained CCyR without progression to advanced disease. Cumulative incidence (CI) of MMR by 12 months showed no significant difference between NIL arm and high-dose IM arm (41.1% vs 28.8, P = 0.334). Only in NIL arm, 2 in 26 (8%) achieved confirmed MR4.0 and UMRD. By 12 months, 10 in 26 (39%), 7 in 26 (27%) and 3 in 16 (19%) patients achieved MMR, in NIL arm, high-dose IM arm and standard-dose IM group respectively. Overall, the patients treated with high-dose IM showed toxicities more frequently, such as leucopenia, anemia, Thrombocytopenia, edema, fatigue, dyspnea and decreased phosphate. In addition, 14 patients in high-dose IM arm have cross-over to NIL treatment due to lack of response (n=11) and intolerance (n=3), and the median duration of NIL treatment was 23 months (range, 2-36 months). Among them, 6 (43%) patients have achieved MMR with a median NIL treatment duration of 12 months (range, 0-18). Conclusions These results demonstrate that early switching to NIL or dose escalation of IM could be recommended, considering the results of standard dose of IM in suboptimal molecular responders. When the tolerability of treatment was considered for switching to NIL or high-dose IM, NIL may be preferred. Through further clinical investigation on a large patient population and longer period observation, the efficacy and safety of early intervention of suboptimal molecular response using NIL or dose escalation of IM will be needed. Updated data with longer follow-up duration will be presented in the meeting. Disclosures: No relevant conflicts of interest to declare.

Brentuximab Vedotin Followed By ABVD in Patients with Previously Untreated Hodgkin Lymphoma. a Pilot Phase II Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3088-3088 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Stefano Luminari ◽  
Francesco Merli ◽  
Emanuela Anna Pesce ◽  
Stephane Chauvie ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Complete Response ◽  
Pilot Phase ◽  
First Line ◽  
Overall Response

Abstract active and well tolerated single agent in the treatment of heavily pretreated Hodgkin lymphoma patients. In this pilot phase II study patients with previously untreated HL underwent sequential regimen consisting in 2 cycles of BV before doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) +/- radiotherapy (RT). The primary endpoint of the study was the response to BV assessed by positron emission tomography (PET) after the 2 cycles (PET2), defined as reduction of Deauville score or, in case of no change in Deauville score, as any reduction in standard uptake value (SUV) intensity compared to basal SUV. Between April and October 2013, 12 patients with a median age at diagnosis of 36 years (range, 19-70), 11 stage I-IIA and 1 stage IIIA, were enrolled. BV was administered as scheduled and at the full dose of 1.8 mg/kg in all patients. After the 2 cycles of BV, the overall response rate was 91%, comprising of ten (83%) complete responses and one (8%) partial metabolic response. The non responding patient had stage III and showed a new lesion at PET2. After ABVD +/- RT, the overall response rate was 100% with 11 complete responses and 1 partial response (converting from progression disease). At a median follow up of 8 months, all 11 patients are still in complete response, while the remaining one relapsed. During BV therapy, the only grade 3 adverse events were transient and asymptomatic increase in liver transaminases (n=3, 25%) and gamma glutamyl transpeptidase (n=2, 17%). During ABVD +/- RT grade III-IV neutropenia occurred in 9 (75%) patients. All toxicities were transient and resolved with growth factor support. Two cycles of BV as first line-treatment in limited stage HL induced an outstanding complete response rate with limited toxicity and reducing the need of chemotherapy. Waiting for a longer follow up to assess the duration of response, our data (sequential administration of immunotherapy and chemotherapy) should be considered the starting point for further studies in first line therapy for limited stage HL patients. Disclosures No relevant conflicts of interest to declare.

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