– Nearly half of all R/R MCL patients in the pooled analysis were able to survive their disease at three years and more than one quarter of patients had no progression in their disease
– Median PFS outcomes were observed to be higher in patients who received ibrutinib earlier and after only one prior therapy
– This analysis comprises of 3.5 years of R/R MCL follow-up data, the longest to date in Bruton’s tyrosine kinase (BTK) inhibition
– This press release corresponds to abstract #151
NORTH CHICAGO, IL, USA I December 9, 2017 I AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced pooled analysis results of the longest follow-up data to date in Bruton’s tyrosine kinase (BTK) inhibition for relapsed/refractory (R/R) mantle cell lymphoma (MCL) patients treated with IMBRUVICA® (ibrutinib). The analysis found that, at three years, 45 percent of patients were able to achieve overall survival (OS) and 26 percent had disease progression-free survival (PFS). The pooled analysis also found that patients who were treated with ibrutinib earlier, after their first relapse/progression, experienced higher rates of OS and PFS.1 The analysis is comprised of data from a total of 370 patients in three different clinical trials: SPARK, RAY and PCYC-1104, and one ongoing Phase 3b extension study, CAN3001, which is eligible to patients who continue to benefit from ibrutinib therapy upon completing a previous ibrutinib clinical trial.2 MCL is an aggressive B-cell malignancy in which most patients relapse after their first line of therapy and receive a poor prognosis.3
These data will be presented in an oral presentation at the 59th Annual American Society of Hematology (ASH) Meeting and Exposition on Dec. 9 at 12:00 p.m. ET in Atlanta (abstract #151).1 IMBRUVICA is a first-in-class BTK inhibitor jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.
“IMBRUVICA continues to provide a beneficial treatment option for patients with relapsed/refractory mantle cell lymphoma,” said Thorsten Graef, M.D., Ph.D., Head of Clinical Development at Pharmacyclics LLC, an AbbVie company. “Prior to the discovery and introduction of IMBRUVICA, people diagnosed with MCL had limited treatment options. This long-term data analysis adds to our growing understanding of IMBRUVICA’s potential treatment benefits for previously-treated MCL patients.”
MCL is one of several subtypes of B-cell non-Hodgkin’s lymphoma (NHL) and represents about six percent (about 4,200) of new cases of NHL each year in the U.S. MCL usually begins with lymph node enlargement and can potentially spread to other tissues such as the bone marrow and liver.3 Median overall survival for MCL patients is three to four years.4
To view all IMBRUVICA company-sponsored or investigator-initiated studies being presented at ASH 2017, which includes 12 oral presentations, please click here.
Abstract #151: Median 3.5-year Follow-Up of Ibrutinib Treatment in Patients with Relapsed/Refractory Mantle Cell Lymphoma: A Pooled Analysis
Oral presentation: Saturday, December 9, 2017, 12:00 PM ET
The pooled analysis includes results from a total of 370 patients from two Phase 2, open-label studies (SPARK and PCYC-1104), one Phase 3, open-label study (RAY), and an additional follow-up of 87 patients across these studies who enrolled in a long-term open-label extension study (CAN3001). Patients enrolled in SPARK, RAY and PCYC-1104 received ibrutinib 560mg orally once daily until progressive disease or unacceptable toxicity. Study inclusion and exclusion criteria were similar across SPARK, PCYC-1104 and RAY, requiring patients to have received at least one prior therapy for MCL and be chemotherapy-free for at least 3 weeks. However, patients in SPARK were required to have already received rituximab and bortezomib, and patients in RAY were required to have already received rituximab. Patients who continued to benefit from ibrutinib therapy at the end of the studies were eligible to enroll in CAN3001, a Phase 3b open-label study, which provides continued access to ibrutinib for patients who have completed an ibrutinib clinical study. Safety reporting in CAN3001 was limited to grade 3/4 adverse events (AEs) and serious adverse events (SAEs). This pooled analysis was limited to patients on ibrutinib therapy, excluding crossover patients. Investigator-assessed tumor response, progression-free survival (PFS), and overall survival (OS) were evaluated. PFS and OS were analyzed by number of prior lines of therapy and best tumor response. Patients in CAN3001 were censored from OS analysis upon treatment or study discontinuation.
With 3.5 years (41 months) of follow-up, the proportion of patients achieving complete response (CR) increased to 26.5%. In addition, 36% (95% CI, 0.31-0.42) and 26% (0.20-0.32) of patients treated with ibrutinib were progression free at 2 and 3 years, respectively, and the median PFS was 13 months. The median PFS in patients with one prior line of therapy was 33.6 (range, 19.4-42.1) months. The median period for patients achieving CR was 46.2 (range, 42.1-not estimable) months. Patients with favorable baseline disease characteristics were more likely to remain on ibrutinib for more than 3 years. Overall, 53% (95% CI, 0.47-0.58), 45% (0.39-0.50), and 37% (0.25-0.49) of patients were alive at 2, 3, and 5 years, respectively, and the median OS was 26.7 months.
In the pooled analysis, the median duration of follow-up was 41.1 months (95% CI, 37.3-42.5) and median exposure to ibrutinib was 11.1 months (range: 0.03-72.1). Eighty-three patients were treated with ibrutinib for 3 or more years, and 40 patients were treated with ibrutinib for 4 or more years. Fifty-four of 87 (62.1%) patients enrolled in CAN3001 remain on ibrutinib. Patients had a median of 2 (range: 1-9) prior lines of therapy before receiving ibrutinib.
Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 79.7% of patients, with the new onset events decreasing after the first year. Cumulative incidence of any major hemorrhage was 7.3%, and new onset events decreased after the first year. The most common grade 3 or higher TEAEs were neutropenia (17.0%), thrombocytopenia (12.2%), pneumonia (11.9%), anemia (9.5%), atrial fibrillation (5.9%) and hypertension (5.1%). Most of these AEs were more common during the first year of ibrutinib treatment. Treatment-emergent SAEs occurred in 61.9% patients and new onset SAEs decreased over time (incidence: 47.3%, 33.9%, 29.6%, 25.3%, and 12.5% for Years 1, 2, 3, 4, and > 4, respectively). The data from this pooled analysis have not been reviewed by the U.S. Food and Drug Administration and they are not in the approved label for IMBRUVICA.
About the U.S. Food and Drug Administration (FDA) Approval of IMBRUVICA to Treat R/R MCL
The FDA approved IMBRUVICA® (ibrutinib) as a single agent for the treatment of adult patients with MCL who have received at least one prior therapy based on the overall response rate (ORR) seen in the Phase 2 study, PCYC-1104, an open-label, multi-center, single-arm trial of 111 previously-treated MCL patients. IMBRUVICA was administered orally at 560-mg once daily until disease progression or unacceptable toxicity. Tumor response was assessed according to the revised International Working Group (IWG) for non-Hodgkin’s lymphoma (NHL) criteria.5 The efficacy results, which were published in the New England Journal of Medicine in 2013, demonstrated a 68% overall response rate with 47% of patients having a partial response and 21% having a complete response. The median duration of response was 17.5 months.5
About IMBRUVICA
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that mainly works by blocking a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells as well as other serious, debilitating conditions.6 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.
IMBRUVICA is FDA-approved in six distinct patient populations: chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), along with previously-treated mantle cell lymphoma (MCL), previously-treated marginal zone lymphoma (MZL) and previously-treated chronic graft-versus-host-disease (cGVHD).7
- IMBRUVICA was first approved for adult patients with MCL who have received at least one prior therapy in November 2013.
- Soon after, IMBRUVICA was initially approved in adult CLL patients who have received at least one prior therapy in February 2014. By July 2014, the therapy received approval for adult CLL patients with 17p deletion, and by March 2016, the therapy was approved as a frontline CLL treatment.
- IMBRUVICA was approved for adult patients with WM in January 2015.
- In May 2016, IMBRUVICA was approved in combination with bendamustine and rituximab (BR) for adult patients with previously treated CLL/SLL.
- In January 2017, IMBRUVICA was approved for adult patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy.
- In August 2017, IMBRUVICA was approved for adult patients with cGVHD that failed to respond to one or more lines of systemic therapy.
Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.
IMBRUVICA has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases.8 IMBRUVICA was one of the first medicines to receive FDA approval via the Breakthrough Therapy Designation pathway.
IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry, with more than 130 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. To date, 90,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.
About AbbVie
AbbVie is a global, research-driven biopharmaceutical company committed to developing innovative advanced therapies for some of the world’s most complex and critical conditions. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook or LinkedIn.
1 Rule, S et al. Median 3.5-year Follow-Up of Ibrutinib Treatment in Patients with Relapsed/Refractory Mantle Cell Lymphoma: A Pooled Analysis. ASH 2017 Abstract #151
2 Dreyling M, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet 2016;387:770-778. Available from: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00667-4/fulltext. Accessed December 2017
3 Leukemia & Lymphoma Society. Mantle Cell Lymphoma Facts. Available from: https://www.lls.org/sites/default/files/file_assets/mantlecelllymphoma.pdf. Accessed October 2017.
4 Herrmann A, Hoster E, Zwingers T, et al. Improvement of overall survival in advanced stage mantle cell lymphoma. J Clin Oncol. 2009;27:511–8.
5 Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1306220#t=article
6 Genetics Home Reference. Isolated growth hormone deficiency. Available from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed July 2017.
7 IMBRUVICA U.S. Prescribing Information, August 2017.
8 U.S. Food and Drug Administration. Fact Sheet: Breakthrough Therapies. Available from: https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm. Accessed November 2017
SOURCE: AbbVie
Post Views: 30
– Nearly half of all R/R MCL patients in the pooled analysis were able to survive their disease at three years and more than one quarter of patients had no progression in their disease
– Median PFS outcomes were observed to be higher in patients who received ibrutinib earlier and after only one prior therapy
– This analysis comprises of 3.5 years of R/R MCL follow-up data, the longest to date in Bruton’s tyrosine kinase (BTK) inhibition
– This press release corresponds to abstract #151
NORTH CHICAGO, IL, USA I December 9, 2017 I AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced pooled analysis results of the longest follow-up data to date in Bruton’s tyrosine kinase (BTK) inhibition for relapsed/refractory (R/R) mantle cell lymphoma (MCL) patients treated with IMBRUVICA® (ibrutinib). The analysis found that, at three years, 45 percent of patients were able to achieve overall survival (OS) and 26 percent had disease progression-free survival (PFS). The pooled analysis also found that patients who were treated with ibrutinib earlier, after their first relapse/progression, experienced higher rates of OS and PFS.1 The analysis is comprised of data from a total of 370 patients in three different clinical trials: SPARK, RAY and PCYC-1104, and one ongoing Phase 3b extension study, CAN3001, which is eligible to patients who continue to benefit from ibrutinib therapy upon completing a previous ibrutinib clinical trial.2 MCL is an aggressive B-cell malignancy in which most patients relapse after their first line of therapy and receive a poor prognosis.3
These data will be presented in an oral presentation at the 59th Annual American Society of Hematology (ASH) Meeting and Exposition on Dec. 9 at 12:00 p.m. ET in Atlanta (abstract #151).1 IMBRUVICA is a first-in-class BTK inhibitor jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc.
“IMBRUVICA continues to provide a beneficial treatment option for patients with relapsed/refractory mantle cell lymphoma,” said Thorsten Graef, M.D., Ph.D., Head of Clinical Development at Pharmacyclics LLC, an AbbVie company. “Prior to the discovery and introduction of IMBRUVICA, people diagnosed with MCL had limited treatment options. This long-term data analysis adds to our growing understanding of IMBRUVICA’s potential treatment benefits for previously-treated MCL patients.”
MCL is one of several subtypes of B-cell non-Hodgkin’s lymphoma (NHL) and represents about six percent (about 4,200) of new cases of NHL each year in the U.S. MCL usually begins with lymph node enlargement and can potentially spread to other tissues such as the bone marrow and liver.3 Median overall survival for MCL patients is three to four years.4
To view all IMBRUVICA company-sponsored or investigator-initiated studies being presented at ASH 2017, which includes 12 oral presentations, please click here.
Abstract #151: Median 3.5-year Follow-Up of Ibrutinib Treatment in Patients with Relapsed/Refractory Mantle Cell Lymphoma: A Pooled Analysis
Oral presentation: Saturday, December 9, 2017, 12:00 PM ET
The pooled analysis includes results from a total of 370 patients from two Phase 2, open-label studies (SPARK and PCYC-1104), one Phase 3, open-label study (RAY), and an additional follow-up of 87 patients across these studies who enrolled in a long-term open-label extension study (CAN3001). Patients enrolled in SPARK, RAY and PCYC-1104 received ibrutinib 560mg orally once daily until progressive disease or unacceptable toxicity. Study inclusion and exclusion criteria were similar across SPARK, PCYC-1104 and RAY, requiring patients to have received at least one prior therapy for MCL and be chemotherapy-free for at least 3 weeks. However, patients in SPARK were required to have already received rituximab and bortezomib, and patients in RAY were required to have already received rituximab. Patients who continued to benefit from ibrutinib therapy at the end of the studies were eligible to enroll in CAN3001, a Phase 3b open-label study, which provides continued access to ibrutinib for patients who have completed an ibrutinib clinical study. Safety reporting in CAN3001 was limited to grade 3/4 adverse events (AEs) and serious adverse events (SAEs). This pooled analysis was limited to patients on ibrutinib therapy, excluding crossover patients. Investigator-assessed tumor response, progression-free survival (PFS), and overall survival (OS) were evaluated. PFS and OS were analyzed by number of prior lines of therapy and best tumor response. Patients in CAN3001 were censored from OS analysis upon treatment or study discontinuation.
With 3.5 years (41 months) of follow-up, the proportion of patients achieving complete response (CR) increased to 26.5%. In addition, 36% (95% CI, 0.31-0.42) and 26% (0.20-0.32) of patients treated with ibrutinib were progression free at 2 and 3 years, respectively, and the median PFS was 13 months. The median PFS in patients with one prior line of therapy was 33.6 (range, 19.4-42.1) months. The median period for patients achieving CR was 46.2 (range, 42.1-not estimable) months. Patients with favorable baseline disease characteristics were more likely to remain on ibrutinib for more than 3 years. Overall, 53% (95% CI, 0.47-0.58), 45% (0.39-0.50), and 37% (0.25-0.49) of patients were alive at 2, 3, and 5 years, respectively, and the median OS was 26.7 months.
In the pooled analysis, the median duration of follow-up was 41.1 months (95% CI, 37.3-42.5) and median exposure to ibrutinib was 11.1 months (range: 0.03-72.1). Eighty-three patients were treated with ibrutinib for 3 or more years, and 40 patients were treated with ibrutinib for 4 or more years. Fifty-four of 87 (62.1%) patients enrolled in CAN3001 remain on ibrutinib. Patients had a median of 2 (range: 1-9) prior lines of therapy before receiving ibrutinib.
Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 79.7% of patients, with the new onset events decreasing after the first year. Cumulative incidence of any major hemorrhage was 7.3%, and new onset events decreased after the first year. The most common grade 3 or higher TEAEs were neutropenia (17.0%), thrombocytopenia (12.2%), pneumonia (11.9%), anemia (9.5%), atrial fibrillation (5.9%) and hypertension (5.1%). Most of these AEs were more common during the first year of ibrutinib treatment. Treatment-emergent SAEs occurred in 61.9% patients and new onset SAEs decreased over time (incidence: 47.3%, 33.9%, 29.6%, 25.3%, and 12.5% for Years 1, 2, 3, 4, and > 4, respectively). The data from this pooled analysis have not been reviewed by the U.S. Food and Drug Administration and they are not in the approved label for IMBRUVICA.
About the U.S. Food and Drug Administration (FDA) Approval of IMBRUVICA to Treat R/R MCL
The FDA approved IMBRUVICA® (ibrutinib) as a single agent for the treatment of adult patients with MCL who have received at least one prior therapy based on the overall response rate (ORR) seen in the Phase 2 study, PCYC-1104, an open-label, multi-center, single-arm trial of 111 previously-treated MCL patients. IMBRUVICA was administered orally at 560-mg once daily until disease progression or unacceptable toxicity. Tumor response was assessed according to the revised International Working Group (IWG) for non-Hodgkin’s lymphoma (NHL) criteria.5 The efficacy results, which were published in the New England Journal of Medicine in 2013, demonstrated a 68% overall response rate with 47% of patients having a partial response and 21% having a complete response. The median duration of response was 17.5 months.5
About IMBRUVICA
IMBRUVICA (ibrutinib) is a first-in-class, oral, once-daily therapy that mainly works by blocking a protein called Bruton’s tyrosine kinase (BTK). BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells as well as other serious, debilitating conditions.6 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.
IMBRUVICA is FDA-approved in six distinct patient populations: chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), along with previously-treated mantle cell lymphoma (MCL), previously-treated marginal zone lymphoma (MZL) and previously-treated chronic graft-versus-host-disease (cGVHD).7
- IMBRUVICA was first approved for adult patients with MCL who have received at least one prior therapy in November 2013.
- Soon after, IMBRUVICA was initially approved in adult CLL patients who have received at least one prior therapy in February 2014. By July 2014, the therapy received approval for adult CLL patients with 17p deletion, and by March 2016, the therapy was approved as a frontline CLL treatment.
- IMBRUVICA was approved for adult patients with WM in January 2015.
- In May 2016, IMBRUVICA was approved in combination with bendamustine and rituximab (BR) for adult patients with previously treated CLL/SLL.
- In January 2017, IMBRUVICA was approved for adult patients with MZL who require systemic therapy and have received at least one prior anti-CD20-based therapy.
- In August 2017, IMBRUVICA was approved for adult patients with cGVHD that failed to respond to one or more lines of systemic therapy.
Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.
IMBRUVICA has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases.8 IMBRUVICA was one of the first medicines to receive FDA approval via the Breakthrough Therapy Designation pathway.
IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA has one of the most robust clinical oncology development programs for a single molecule in the industry, with more than 130 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. To date, 90,000 patients around the world have been treated with IMBRUVICA in clinical practice and clinical trials.
About AbbVie
AbbVie is a global, research-driven biopharmaceutical company committed to developing innovative advanced therapies for some of the world’s most complex and critical conditions. The company’s mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook or LinkedIn.
1 Rule, S et al. Median 3.5-year Follow-Up of Ibrutinib Treatment in Patients with Relapsed/Refractory Mantle Cell Lymphoma: A Pooled Analysis. ASH 2017 Abstract #151
2 Dreyling M, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet 2016;387:770-778. Available from: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)00667-4/fulltext. Accessed December 2017
3 Leukemia & Lymphoma Society. Mantle Cell Lymphoma Facts. Available from: https://www.lls.org/sites/default/files/file_assets/mantlecelllymphoma.pdf. Accessed October 2017.
4 Herrmann A, Hoster E, Zwingers T, et al. Improvement of overall survival in advanced stage mantle cell lymphoma. J Clin Oncol. 2009;27:511–8.
5 Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1306220#t=article
6 Genetics Home Reference. Isolated growth hormone deficiency. Available from: http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed July 2017.
7 IMBRUVICA U.S. Prescribing Information, August 2017.
8 U.S. Food and Drug Administration. Fact Sheet: Breakthrough Therapies. Available from: https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/ucm329491.htm. Accessed November 2017
SOURCE: AbbVie
Post Views: 30
