PROPEL Study Reinforces Viability of Pralatrexate in Peripheral T-cell Lymphoma; Cost Questioned

December 8, 2009
Christina T. Loguidice

During the 51st ASH Annual Meeting, several new data from the PROPEL trial were released, including updates on the ORR and safety of pralatrexate in patients with PTCL and data on the correlation between baseline methylmalonic acid status and mucositis severity in this population. While the data reinforce pralatrexate as a viable treatment in patients with relapsed or refractory PTCL, some question whether the drug confers enough of a benefit to warrant its $30,000 per month cost.

New Orleans, LA — In September 2009, the FDA granted accelerated approval for pralatrexate (pralatrexate) as a single agent to treat patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Approval was based on the overall response rate (ORR) observed for this agent; clinical benefit has yet to be demonstrated. Pralatrexate is currently the only drug approved by the FDA for this indication. During the 51st ASH Annual Meeting, several new data from the PROPEL trial were released, including updates on the ORR and safety of pralatrexate in patients with PTCL and data on the correlation between baseline methylmalonic acid status and mucositis severity in this population. While the data reinforce pralatrexate as a viable treatment in patients with relapsed or refractory PTCL, some question whether the drug confers enough of a benefit to warrant its $30,000 per month cost.

PROPEL Overall Response

In a poster session, Kerry Savage, MD, British Columbia Cancer Agency, Vancouver, British Columbia, Canada, discussed the responses to pralatrexate in patients enrolled in PROPEL who were considered to have refractory PTCL, defined as no evidence of response to their most recent treatment or to any other prior therapies. These patients were heavily pretreated, having undergone a median of 3 prior systemic therapies; CHOP or another multi-agent chemotherapy regimen were the most common. Of the 109 evaluable patients included in the analysis, 69 patients (63%) had shown no evidence of response to their most recent prior treatment. Once they received pralatrexate, 17 patients achieved a response, for a 25% ORR. The duration of response ranged from 41 days to 673 days. An investigator review found that 25 patients achieved response, for an ORR of 36%. When central review assessed patients (n = 26) who had not demonstrated any evidence of response to any prior therapy, they found that 19% (n = 5) responded to pralatrexate, with a duration ranging from 54 to 306 days. The investigator review found that 27% (n = 7) had responded.

Dr Savage noted that pralatrexate demonstrates activity in patients with PTCL who are refractory to their most recent therapy, including those who have been refractory to all prior therapies. He said the findings suggest that pralatrexate can overcome mechanisms of drug resistance in this patient population.

.

ASH Abstract 1678

PROPEL Safety Data

A poster presented by Lauren Pinter-Brown, MD, University of California at Los Angeles, outlined three important safety parameters, including duration of pralatrexate treatment, early- and late-onset pralatrexate toxicities, and the effect of pralatrexate dose modification on toxicities. A total of 111 patients received pralatrexate and were evaluable for safety. The most common adverse events included mucosal inflammation, nausea, thrombocytopenia, and fatigue. Although patients had received a median of 3 prior systemic therapies with agents that have potential organ toxicities, the majority of patients tolerated the full dose of pralatrexate (30 mg/m

). Protocol-specified dose modification schema effectively reduced the occurrence of mucosal inflammation, and adherence to these guidelines permitted patients to continue on pralatrexate therapy. The most common grade 3-4 adverse effects for patients who initiated cycle 3 were apparent at similar or lower rates compared with those observed in cycles 1 and 2, suggesting there is no cumulative-dose toxicity with pralatrexate. According to Dr Brown, these data suggest that pralatrexate is well tolerated and safe in patients with PTCL.

.

2ASHAbstract 1675

Baseline MMS Status and Mucositis Severity

A poster presented by Barbara Pro, MD, the University of Texas M.D. Anderson Cancer Center, Houston, evaluated baseline methylmalonic acid (MMA) status, homocysteine, and red blood cell folate levels in 111 patients enrolled in PROPEL who were evaluable for safety. Dr Po and colleagues found that the maximum mucosal inflammation grade experienced during pralatrexate therapy (grade 0 vs grade 1-2 vs grade 3-4) and the baseline MMA value had a statistically significant linear relationship (

= .039). Baseline homocysteine and red blood cell folate values were not predictive of the severity of mucositis or thrombocytopenia in this assessment. There was also a trend toward a relationship between increasing MMA and increasing severity of thrombocytopenia, but this relationship was not found to be statistically significant.

P

Dr Po and colleagues concluded that because patients with relapsed or refractory PTCL may have poor nutritional status, all patients treated with pralatrexate, including those with elevated MMA, should receive vitamin supplementation. Studies investigating the relationship between MMA levels and the development of mucositis and thrombocytopenia among patients treated with pralatrexate may be warranted.

.

ASH Abstract 1681

All investigators are affiliated with Allos Therapeutics.

Disclosures: