Efficacy of Short Oral Leucovorin Rescue (SOLR) In Managing Recurrent Pralatrexate (Folotyn) Induced Mucositis (RPIM) Despite Dose Reduction

Abstract 4745

Mucositis is a frequent complication experienced by patients receiving weekly Pralatrexate, an antifolate agent, which often leads to significant morbidity, decreased quality of life, and early discontinuation of this active therapy in aggressive and almost universally fatal Peripheral T-cell Lymphomas (PTCL). Despite its frequency, there is no standard medical management currently except omitting doses followed by one step dose reduction and subsequent discontinuation, many times despite notable responses. Since Leucovorin is approved as antidote for Pralatrexate overdose, we reviewed our clinical experience with its reactive (not pre-emptive) use in our PTCL patients with Grade 2+ RPIM that have already gone through dose omissions and dose reductions and had no other alternative but to discontinue therapy. SOLR consisted of 25 mg po Q6h for 5 days the week of RPIM to be stopped at least 48hours prior to the planned subsequent weekly dose. We reviewed our experience with such approach which amounted to 17 such interventions. All 17 SOLR regardless of grade lead to resolution of subjective symptoms by the 7^th day with time to initial subjective improvement at around the 4^th day from SOLR initiation. Sixteen SOLR interventions had complete resolution of RPIM on exam on the 7^th day and one had almost complete resolution. As such, all cases were ready to resume weekly recommended dosing per standard PTCL regimen. None of SOLR patients discontinued Pralatrexate for RPIM. None of SOLR patients lost their response attained prior to the intervention. In fact, the patient with transformed Mycosis Fungoides continued to show notable further skin response. When compared to the PROPEL Trial which used dose omission and delay to address mucositis, SOLR further shortened the time to resolution by 3–5 days (7 days vs. median of 10 days for Grade 2 and 12 days for Grade 3- Allos unpublished data).

Although further controlled studies are recommended, our clinical observation suggests that reactive SOLR intervention in RPIM offers rapid and effective symptom management by aiding faster mucosal healing and further decreases drug holidays and discontinuation of therapy without any discernable compromise in efficacy.