Brentuximab Vedotin is Active and Well Tolerated in Patients 60 Years of Age or Older With HL

• Interim results of ongoing, nonrandomized, open-label phase II study [1]
Summary of Key Conclusions
• Brentuximab vedotin induces ORR of 89% and CR of 63% in patients with Hodgkin’s lymphoma (HL) 60 years of age or older
    o Well tolerated in the elderly patient population (median age: 78 years)
• 100% of patients experienced reduction in size of target lesions
• Investigation of combination treatment being considered to further investigate the safety and efficacy of alternative regimens for elderly patients with HL
Background
• Older age (older than 60 years of age) associated with inferior prognosis in patients with newly-diagnosed HL[2]
• Comorbidities in the elderly[3]
    o Increased treatment-related toxicity
    o Interference with delivery of standard-intensity chemotherapy
    o Limited treatment durations
• Studies suggest brentuximab vedotin, an anti-CD30 antibody conjugated to monomethyl auristatin E (microtubule-disrupting agent), has efficacy against relapsed HL and systemic anaplastic large cell lymphoma, and has efficacy in patients 60 years of age or older with relapsed or refractory HL similar to that of younger patients[4-6]
• Current Phase II study (NCT01716806) evaluates efficacy, tolerability, and safety of brentuximab vedotin in HL patients 60 years of age or older
Summary of Study Design
• Treatment: Brentuximab vedotin
    o 1.8 mg/kg intravenously on Day 1 of each 21-day cycle
    o Up to 16 cycles
• Design: Pretreatment (28 Days)
    o Screening/baseline of patients
    o Perform computed tomography (CT) and positron emission tomography (PET) on patients
    o Response assessment performed

•  Baseline/screening
•  Cycles 2, 4, 8, 12
•  End of treatment (EOT)
•  Every 3 months in follow-up
•  PET performed at cycles 2, 8, and EOT

• Patients with at least SD at time of restaging (or EOT)
    o Additional cycles of brentuximab vedotin allowed
    o Option to continue study beyond cycle 16 (CT at end of cycle 16)
• Survival: followed every 3 months until withdrawal of consent, death or study closure
• Patients who have not progressed at follow-up will have response assessments at least every 6 months for 2 years followed by annual evaluations
• Key eligibility
    o Untreated patients with classical HL (stage I-IV)
    o 60 years of age or older
    o ECOG performance status <= 3
    o Declined or ineligible for conventional combination chemotherapy
Baseline Characteristics
• Elderly population; median age: 78 years (range: 64-92)

Description of Current Analysis
• Primary objectives
    o ORR of brentuximab vedotin as first-line treatment in older patients 60 years of age or older according to Revised Response Criteria for Malignant Lymphoma
    o Safety and tolerability
    o Duration of objective response
    o PFS
    o OS
Main Findings
• Antitumor activity: 89% efficacy-evaluable patients achieved objective response
    o CR: 12 patients
    o PR: 5 patients
    o 2 patients had maximal response of SD
    o Median decrease in standardized uptake value (SUVmax) after 2 cycles: 85% (n = 18)
• Tumor reduction achieved in 100% of patients

• Treatment-related AEs: observed in 15 of 19 patients
• Majority of AEs grade <= 2 with exception of peripheral sensory neuropathy, rash, neutropenia, orthostatic hypotension (n = 1 each, all grade 3)

• Other safety information
    o AEs that lead to treatment discontinuation

• Orthostatic hypotension (n = 1)
• Peripheral motor neuropathy (n = 1)

    o Serious AEs

• Orthostatic hypotension (n = 1)
• Pyrexia (n = 1)

    o No on-study deaths have occurred to date
    o Preexisting peripheral sensory neuropathy: 5 patients

• 3 of the 5 have had no worsening of neuropathies after receiving brentuximab vedotin

• No Grade 4 laboratory abnormalities to date

• AEs occurring in >=10% of patients, regardless of relationship to study treatment
Other Outcomes
• Median duration of treatment: 18 weeks

References
1. Yasenchak A, Chen R, Sharman J, et al. A phase 2 study of single-agent brentuximab vedotin for front-line therapy of hodgkin lymphoma in patients age 60 years and above: interim results. Program and abstracts of the 55th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2013; New Orleans, Louisiana. Abstract 4389.
2. Evens AM, Hong F, Gordon LI, et al. The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. Br J Haematol. 2013;161:76-86.
3. Evens A, Helenowski I, Ramsdaleet E, et al. A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era. Blood. 2012;119:692-693.
4. Younes A, Gopal A, Smith S, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30:2183-2189.
5. Pro B, Advani R, Brice P, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012;30:2190-2196.
6. Fanale MA, Bartlett NL, Forero-Torres A, et al. Retrospective analysis of the safety and efficacy of brentuximab vedotin in patients aged 60 years or older with relapsed or refractory CD30+ hematologic malignancies. Blood. 2012;120. Abstract 3687.