Ipilimumab for advanced, refractory melanoma: A report of the Israeli cohort of expanded access program.

e20039 Background: As the first agent to show survival advantage in metastatic melanoma, Ipilimumab (Yervoy, BMS) is being gradually introduced into health services worldwide. It's unique immune mediated side effects requires the incorporation of follow-up guidelines to prevent toxic sequella. We report on safety and efficacy results of refractory melanoma patients (pts) treated on an international expanded access program of Ipilimumab. Methods: Between 4/2010 and 12/2011 183 pts were treated. Pts received Ipilimumab 3 mg/kg q3w for 4 doses. Pts with evidence of clinical benefit at week 12 (CR, PR or SD), were eligible for re-induction upon progression. Results: All pts were pretreated for metastatic disease (median:1 line,range 1-5). 140 pts(77%) had M1c disease, 63 pts(34%) had brain metastasis and 84 (46%) had LDH above ULN, reflecting poor prognostic characteristics of this cohort. Patients received 3.6 doses of Ipilimumab on average. 11% received less than 4 cycles due to toxicity. Grade 3/4 immune-related adverse events were noted in 19.6% with the most common all grades toxicity being diarrhea (17.5%), pruritus (14%) rash (13%) and fatigue (8.7%). Grade 5 toxicity was noted in 4 patients (2%). Five pts were treated with anti TNF antibodies (Infliximab) for steroid resistant toxicity. Objective responses were noted in 16 pts (8.7%;4 CR, 12 PR), 26 pts(14.2%) had stable disease, overall yielding clinical benefit in 23%. Patients with stage IIIc, M1a and M1b were more likely to benefit (52% Vs 23% of the group, p<0.001) as well as patients previously treated by immunotherapy (p=0.026). Median OS was 9.2 months with 1 year survival of 42%. 34 pts (18.6%) are alive beyond 20 months, the majority of them received no further treatment. Factors favoring survival included stage IIIc, M1a and M1b, LDH below ULN and lymphocyte count at week 6 above 1000/ml (p values: <0.001,<0.001, 0.03 respectively). None of the 14 ocular melanoma pts exhibited clinical benefit. Conclusions: Our cohort reflects rapid adoption of this new modality. Ipilimumab had significant clinical benefit, comparable with previous reports, in a heterogenous group of patients, including those with poor prognostic factors.

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Clinical Benefit in NSCLC: Advanced-Stage Patients Require Symptom-Improving Palliation. Experiences from the ‘Iressa’ Expanded Access Program

Oncology Research and Treatment ◽

10.1159/000084204 ◽

2005 ◽

Vol 28 (4) ◽

pp. 195-198 ◽

Cited By ~ 5

Author(s):

Wolfgang Schuette ◽

Sylke Nagel ◽

Steffen Schaedlich ◽

Daniel Brust ◽

Thomas Blankenburg

Keyword(s):

Clinical Benefit ◽

Advanced Stage ◽

Expanded Access ◽

Expanded Access Program ◽

Access Program

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Expanded Access Program (EAP) for Lenalidomide (Revlimid®) Plus Dexamethasone in over 1400 Subjects with Relapsed or Refractory Multiple Myeloma.

Blood ◽

10.1182/blood.v108.11.3556.3556 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3556-3556 ◽

Cited By ~ 2

Author(s):

Christine Chen ◽

Donna E. Reece ◽

David Siegel ◽

Ruben Niesvizky ◽

Ralph Vincent Boccia ◽

...

Keyword(s):

Multiple Myeloma ◽

Phase Iii ◽

Advocacy Groups ◽

Refractory Multiple Myeloma ◽

Expanded Access ◽

Prior Therapy ◽

Expanded Access Program ◽

The Us ◽

Grade 3 ◽

Access Program

Abstract Background: Lenalidomide (Revlimid®) in combination with dexamethasone was approved in the US on June 29, 2006 for the treatment of subjects with multiple myeloma who had received at least one prior therapy. On February 28, 2005 based upon a positive interim analysis of two pivotal placebo-controlled Phase III studies, an independent Data Safety Monitoring Board recommended the studies be unblinded and all subjects in both studies be given access to lenalidomide. In April 2005, the FDA in association with myeloma patient advocacy groups requested Celgene establish an expanded access program to make lenalidomide plus dexamethasone available to subjects with relapsed or refractory multiple myeloma while the treatment was awaiting approval. Aim: To provide lenalidomide to multiple myeloma subjects with a high likelihood of benefit and to obtain additional safety data. Methods: Subjects with relapsed or refractory multiple myeloma that received at least 1 prior therapy were eligible. Subjects received 25 mg lenalidomide plus high-dose dexamethasone in 4-week cycles until disease progression was documented, study drug was discontinued, or lenalidomide became commercially available for this indication. Results: Between September 8, 2005 and July 25, 2006, approximately 1400 subjects in the US and Canada were enrolled into the study. A data snapshot taken March 17, 2006 demonstrated that 746 subjects had been enrolled, median age was 63 years, 60% were male, and 66.5% had Stage III disease. Median time on study was 7.1 weeks (0.1–24.4) and median daily dose was 20.5 mg. At least one Grade 3 or 4 adverse event was reported in 261 (35%) of the 746 subjects. Most commonly reported Grade 3–4 events were neutropenia (7.9% of subjects), thrombocytopenia (6.0%), fatigue (3.6%), anemia (3.5%), pneumonia (3.1%) and hyperglycemia (2.0%). These most commonly reported Grade 3–4 adverse events were the same as those found in the previous pivotal studies, however, their frequencies of occurrence were lower in the current study probably due to ongoing data collection and differences in study maturity. Likewise, the most commonly reported adverse events (all grades) were the same as those reported in the two previous pivotal studies. Conclusion: Preliminary data from this expanded access program in over 1400 subjects with multiple myeloma are consistent with results from two earlier Phase III pivotal studies. The EAP of lenalidomide plus dexamethasone in multiple myeloma represents a model of how government, advocacy groups, healthcare providers and industry can work together to quickly provide treatment to subjects in need while a clearly active treatment regimen is awaiting approval.

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