determine dose limiting toxicities of Peg-IFN-α-2b. Secondary end points were the number of patients exhibiting complete remission (CR) and duration of response. Response was assessed according to the Composite Assessment of Index Lesion Disease Severity (CAILS). During dose escalation phase patients were monitored for side effects every other week and in maintenance phase response was assessed every 4 weeks. The median duration of weekly PEG-IFN-α-2b injections received was 10 weeks (2–40 weeks) with an average dose of 3.76 μg/kg. Median phototherapy duration was 12 weeks (2–48 weeks).
While 5/7 patients met criteria for response including one with CR, the median progression free survival was 3.5 months (0.5–10.0 months; Table1). Early termination of study protocol occurred in all cases and reasons were disease progression (2/7), side effects (1/7), or both (3/7) (Table1). All patients had constitutional symptoms and hematologic abnormalities (Table 2). With a median follow up of 34 months (5–135 months), 6/7 patients died, with 5/6 attributed to disease. The only patient (case 5) still alive (>10–year survival) is currently undergoing treatment for transformed MF IVB.
This study was designed as a feasibility trial with intra-patient dose escalation permitted. Efficacy estimates are limited by the sample size and treatment interruptions due to PEG-IFN-α-2b side effects. All patients experienced side effects, which resulted in either treatment interruption or complete discontinuation and we therefore conclude that the administered PEG-IFN-α-2b dose was too high. Today PEG-IFN-α-2b is dosed at 1.5 μg/kg and has been shown to be most effective and safe.4 However, during the time the study was conducted, it was common practice to increase unpegylated interferon dose as permitted by side effects.5 Still, the short duration of response suggests that high dose PEG-IFN-α-2b and phototherapy may not be considered a viable treatment option for advanced stages of MF/SS, especially with large cell transformation, at least in our study.1
In conclusion, in this small clinical trial with advanced stage MF/SS, five of seven patients showed response to high dose pegylated interferon in combination with phototherapy with the most common reason for discontinuation being hematologic toxicity and disease progression. Lower doses of pegylated IFN with phototherapy is likely to be a more efficacious and tolerable strategy.5 Nevertheless, interferons in combination with phototherapy are indispensable therapeutics in the treatment of MF and therefore Merck’s recent announcement of future discontinuation of IFN-α-2b and PEG-IFN-α-2b poses a serious challenge to the treatment of CTCL.
While 5/7 patients met criteria for response including one with CR, the median progression free survival was 3.5 months (0.5–10.0 months; Table1). Early termination of study protocol occurred in all cases and reasons were disease progression (2/7), side effects (1/7), or both (3/7) (Table1). All patients had constitutional symptoms and hematologic abnormalities (Table 2). With a median follow up of 34 months (5–135 months), 6/7 patients died, with 5/6 attributed to disease. The only patient (case 5) still alive (>10–year survival) is currently undergoing treatment for transformed MF IVB.
This study was designed as a feasibility trial with intra-patient dose escalation permitted. Efficacy estimates are limited by the sample size and treatment interruptions due to PEG-IFN-α-2b side effects. All patients experienced side effects, which resulted in either treatment interruption or complete discontinuation and we therefore conclude that the administered PEG-IFN-α-2b dose was too high. Today PEG-IFN-α-2b is dosed at 1.5 μg/kg and has been shown to be most effective and safe.4 However, during the time the study was conducted, it was common practice to increase unpegylated interferon dose as permitted by side effects.5 Still, the short duration of response suggests that high dose PEG-IFN-α-2b and phototherapy may not be considered a viable treatment option for advanced stages of MF/SS, especially with large cell transformation, at least in our study.1
In conclusion, in this small clinical trial with advanced stage MF/SS, five of seven patients showed response to high dose pegylated interferon in combination with phototherapy with the most common reason for discontinuation being hematologic toxicity and disease progression. Lower doses of pegylated IFN with phototherapy is likely to be a more efficacious and tolerable strategy.5 Nevertheless, interferons in combination with phototherapy are indispensable therapeutics in the treatment of MF and therefore Merck’s recent announcement of future discontinuation of IFN-α-2b and PEG-IFN-α-2b poses a serious challenge to the treatment of CTCL.
DISCLOSURES
The authors have no conflict of interest to declare.
Funding: Partially funded by Schering-Plough.
IRB approval status: Reviewed and approved by NU IRB; approval IRB #: STU00002993-MODCR0002
Clinicaltrials.gov listing: NCT00724061
Funding: Partially funded by Schering-Plough.
IRB approval status: Reviewed and approved by NU IRB; approval IRB #: STU00002993-MODCR0002
Clinicaltrials.gov listing: NCT00724061
REFERENCES
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- Yanagi T, Shimizu T, Ujiie H, et al. Peginterferon alfa-2b for mycosis fungoides. Arch Dermatol. May 2006;142(5):649-51. doi:10.1001/ archderm.142.5.649
- Husken AC, Tsianakas A, Hensen P, et al. Comparison of pegylated interferon alpha-2b plus psoralen PUVA versus standard interferon alpha-2a plus PUVA in patients with cutaneous T-cell lymphoma. J Eur Acad Dermatol Venereol. Jan 2012;26(1):71-8. doi:10.1111/ j.1468-3083.2011.04011.x
- Spaccarelli N, Rook AH. The Use of Interferons in the Treatment of Cutaneous T-Cell Lymphoma. 2015;33(4):731-745. doi:10.1016/j. det.2015.05.008
- Olsen EA. Interferon in the treatment of cutaneous T-cell lymphoma. Dermatol Ther. 2003;16(4):311-21. doi:10.1111/j.1396- 0296.2003.01643.x
AUTHOR CORRESPONDENCE
Christina J. Walker MD christina.walker@northwestern.edu
