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ASH 2013: Early suggestion of cure in Hodgkin lymphoma patients treated with brentuximab vedotin

12 Dec 2013
ASH 2013: Early suggestion of cure in Hodgkin lymphoma patients treated with brentuximab vedotin

At three years follow-up, patients with relapsed or refractory Hodgkin lymphoma (HL) following autologous stem cell transplant (auto-SCT) achieved a median overall survival of 40.5 months with brentuximab vedotin, reported a study at the American Society of Hematology meeting, held in New Orleans, 7-10 December 2013.

The investigators furthermore found that 14 of these heavily pre-treated patients showed no evidence of progression.

For patients with relapsed or refractory HL the standard of care has been salvage chemotherapy followed by auto-SCT, which induces long-term remission in around 50% of patients.

For those who experience relapse or progressive HL within one year of auto-SCT prognosis has been poor, with a median survival of approximately 1.2 years.

“This relatively young population has had no available standard of care and represents an urgent unmet medical need,” commented Professor Anton Hagenbeck, from the Academic Medical Centre, Amsterdam.

Brentuximab vedotin, the first new drug for HL in more than 30 years, drug comprises an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristain E (MMAE).

The linker system complex has been designed to be stable in the blood stream, but to release MMAE upon internalization into CD30 expressing tumour cells.

“For HL cells this conjugate represents a wolf in sheep’s clothing. Key to success has been the strengthened linker system preventing the complex from breaking down outside the cell resulting in less systemic toxicity and high efficacy,” explained Hagenbeck.

Brentuximab vedotin received accelerated approval from the FDA in August 2011, and conditional marketing authorisation from the European Commission in October 2012.

The current analysis by Ajay Gopal from the University of Washington/Fred Hutchinson Cancer Research Center, Seattle, UK, and colleagues represents an update of the phase 2 pivotal study (JCO: 2012, 30:2183-2189).

The investigators set out to determine the efficacy and safety of brentuximab vedotin in 102 patients with relapsed or refractory HL following auto-SCT.
The patients, who had a median age of 31 years, received 1.8 mg/kg brentuximab vedotin every three weeks as 30 minute outpatient infusions for up to 16 cycles.
Results show that median overall survival for patients receiving brentuximab vedotin was 40.5 months (95% CI: 28.7, -[range, 1.8to 48.3 months]), a result that can be compared to a retrospective multicentre series of patients relapsing after auto-SCT, showing a median overall survival of 2.4 years (Leuk. Lymphoma 2013, 54:2531-2533).

Additionally, the estimated three-year survival for the current study was 54% (95% CI:44-64%), and at a median of 32.7 months (range 1.8 to 48.3 months) since first dose brentuximab vedotin 50% (51 of 102) patients were alive.

Furthermore, 18 patients remained in remission according to investigator review, and 14 patients according to central independent review.

“It could even be these patients are cured because we know in this high risk group responders are likely to relapse in two years,” commented Hagenbeck.
In a second study (also presented at ASH), Barbara Pro from the Fox Chase Cancer Center, Philadelphia, PA, and colleagues, set out to determine the efficacy of brentuximab vedotin in 52 patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL).

In sALCL there is also an unmet medical need since approximately 40-65% of patients develop recurrent disease after frontline treatment.
For these patients, who have a median overall survival of seven months, there has been no defined standard of care.


Patients received 1.8mg/kg IV every 21 days administered over 30 minutes in outpatients.


As previously reported the overall response rate was 86% (50 of 58 patients) and the complete response rate was 59% (34 of 58 patients) (CI 75-94).
The current analysis showed that with a median observation time from first dose of 33.4 months, the median duration of objective response for all patients was 13.2 months; and for patients obtaining a complete response the median duration of response was 26.3 months.


Of the 34 patients who achieved a complete response, 16 (47%) remained in remission at the time of analysis.


The estimated three year survival rate was 63% (95% CI: 51% -76%), while the median overall survival for patients obtaining a complete response has yet to be reached.


Three phase 3 trials of brentuximab vedotin are currently ongoing, in frontline HL, front line mature T-cell lymphoma, and high risk post-transplant HL patients.


Reference


A K Gopal, R Chen, S Smith, et al. The three-year follow-up data and characterization of long-term remissions from an ongoing Phase 2 study of Brentuximab Vedotin in patients with relapsed or refractory Hodgkin Lymphoma. Abstract number 4382.

B Pro, R Advani, P Brice, et al. Three year survival results from an ongoing phase 2 study of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma. Abstract number 1809.