Palifermin as Primary Mucositis Prophylaxis in Patients with B-Cell Non-Hodgkin Lymphoma: A Case Series

To the Editor:

Progress continues to be made regarding the treatment of children and adolescents with aggressive B-cell Non-Hodgkin Lymphoma (NHL). Recent data demonstrated patients with mature B-cell NHL have an improved overall survival with the addition of rituximab to lymphomes malins B (LMB) chemotherapy as part of ANHL1131.¹ The results are very promising but there should still be awareness of therapy-related adverse events. The second most common therapy-related adverse event in this study was oral mucositis with grade 3 oral mucositis occurring in 71% of patients.¹ This is likely due to the combination of high-dose methotrexate and doxorubicin.² Complications related to mucositis may include severe pain requiring opioids, nutritional deficiencies necessitating parenteral nutrition, life-threatening bloodstream infections, and prolonged hospitalizations.³ Proper oral care is the standard first-line approach to mucositis prevention but its benefits may be limited with more intensive chemotherapy regimens.

Palifermin, a human recombinant keratinocyte growth factor, is approved by the Food and Drug Administration to decrease the incidence of oral mucositis associated with hematopoietic stem cell transplantation (HSCT). It has also shown positive effects on reducing mucositis frequency and severity in children receiving cancer therapy.^4,5 Liu et al² evaluated the use of palifermin as secondary mucositis prophylaxis in non-HSCT pediatric patients, including those with NHL. Patients had less reoccurrence of mucositis, decreased opioid and antibiotic use, and decreased duration of hospitalization. Single dose palifermin was also utilized as the pharmacokinetic profile is comparable to standard dose for adult patients.^6,7 Here we describe our experience with single dose palifermin as primary mucositis prophylaxis in two patients receiving therapy per Group B and Group C1 (CSF negative) of ANHL1131. Patients in both groups receive initial therapy with cyclophosphamide, vincristine, and prednisone (COP) followed by 4-6 cycles of additional chemotherapy as well as intrathecal chemotherapy. After completion of COP patients in Group B receive two cycles of rituximab, cyclophosphamide, vincristine, prednisone, doxorubicin, and high dose methotrexate (R-COPADM) followed by two cycles of rituximab, cytarabine, and high dose methotrexate (R-CYM). After completion of COP patients in Group C1 (CSF negative) receive two cycles of R-COPADM followed by two cycles of rituximab, cytarabine, high dose cytarabine, and etoposide (R-CYVE). After completion of R-CYVE patients receive one cycle of COPADM followed by one cycle of cytarabine and etoposide.

The first patient was a 19 year old male with Stage II diffuse large B-cell lymphoma (DLBCL) treated per Group B of ANHL1131. He received a single dose of palifermin 180 mcg/kg in the outpatient setting three days prior to the first two cycles of R-COPADM. He did not receive palifermin prior to cycle 3, R-CYM, due to the perceived lower risk of mucositis. But after developing grade III mucositis 7 days after cycle 3, palifermin was reinstituted prior to cycle 4, R-CYM. Of the three cycles where palifermin was used, there was no need for intravenous (IV) opioid therapy, parenteral nutrition, or hospitalization due to mucositis. Each of four doses of methotrexate was 3 g/m² IV administered over 4 hours. The patient did not experience any delays in methotrexate clearance or significant changes in renal function, post-hydration, or leucovorin dosage. He remains in complete remission one year post-therapy.

The second patient was a 16 year old female with Burkitt lymphoma treated per Group C1 (CSF negative) of ANHL1131. She received a single dose of palifermin 180 mcg/kg in the outpatient setting 3 days prior to all 6 cycles of chemotherapy. She did not have mucositis or require opioids, parenteral nutrition, or hospitalization due to mucositis throughout treatment. Each of the three doses of methotrexate was 8 g/m² IV administered over 4 hours. The patient did experience a delay in methotrexate clearance after the first cycle of R-COPADM as it took 120 hours to achieve a level of < 0.15. No significant changes occurred in renal function, post-hydration, or leucovorin dosage during subsequent cycles of high dose methotrexate. She has no evidence of disease at end of therapy.

No toxicities from palifermin were noted in either patient. Adverse events related to palifermin are mainly limited to rash, pruritus, erythema, taste alteration, and increased thickness of oral mucosa, tongue, and lips. These adverse events are typically mild to moderate in severity and transient.³

Mucositis can be a significant cause of morbidity in these patients and despite improved disease related outcomes better supportive care measures are needed. We recently evaluated mucositis related complications around COPADM cycles in 16 patients and 14 of them were readmitted for mucositis related complications.⁸ Patients that were readmitted required scheduled opioids for an average of 6 days per admission, 6 patients required parenteral nutrition, and their average length of stay was 8 days. This experience along with the data from Liu et al² led us to utilizing palifermin in an effort to ameliorate these complications. Our practice establishes precedent for the use of palifermin for primary mucositis prophylaxis as a supportive care strategy in patients with NHL receiving therapy per ANHL1131. Prospective studies are warranted to confirm the benefit and safety of palifermin compared to other prevention strategies such as oral saline rinses or a standardized oral mouth care protocol.