- 05/2021 acrolentiginous melanoma of the left foot
- Initial stage: T4bN3bM1b, IV (AJCC 2017), BRAF wild-type
- Inguinal and iliac lymph node metastases
- One metastasis in small pelvis
- 06/2021 – 08/2021: Combination immunotherapy with ipilimumab (3 mg/kg bw) and nivolumab (1 mg/kg bw) every three weeks
- 08/2021 – 11/2021: Interruption of immunotherapy due to irPneumonitis grade 1 and irHepatitis grade 3
- 11/2021 – 01/2022: Nivolumab 240 mg every two weeks
After 4 doses of combination immunotherapy with ipilimumab and nivolumab, a chest CT performed for staging showed a nonspecific interstitial pneumonia (NSIP)-pattern. The patient was completely asymptomatic (no dyspnoea, malaise, cough or fever). We diagnosed irPneumonitis grade 1 (CTCAE). In the follow-up laboratory check, AST and ALT were elevated > 5 x ULN. Therefore, in addition irHepatitis grade 3 (CTCAE) was diagnosed.
The immunotherapy was interrupted. Therapy with methylprednisolone 1.5 mg/kg bw for three days was initiated and tapered over the following weeks. The transaminases declined and the pulmonary radiological findings clearly improved. The patient remained asymptomatic at all times.
After normalization of transaminases, we reinitiated monotherapy with nivolumab 240 mg every two weeks. To date, the patient has received five doses of nivolumab and has remained asymptomatic. The transaminases remained within the normal range.
A rechallenge with immunotherapy carries the risk of reexacerbation of the irAE but may be indicated in certain circumstances.
Pollack et al. studied 80 patients who had to interrupt combined immunotherapy due to an irAE. Of those patients 39% experienced recurrent (18%) or clinically significant distinct (21%) irAE with anti-PD-1 monotherapy resumption. In this study, recurrence of irAE was independent of the duration of steroid taper, use of other immunosuppressants in addition to steroids, and the severity of the initial irAE. Under rechallenge with anti-PD1 monotherapy, a complete or partial response was observed in 70% of the patients, a stable disease in 19% and a progressive disease in 11% (Pollack et al, Ann Oncol., 2018).
Patients who are rechallenged show a reexacerbation in about a third of the cases if challenged with the same immunotherapy (Abu Seibh et al, J Clin Oncol., 2019) and 18% if challenged with monotherapy after combination immunotherapy. Thus, a rechallenge with immunotherapy can be considered in side effects that are not life-threatening, as there is a high probability of good efficacy. Patients have to be informed about the risk of reexacerbation. Clinicians should use critical judgement and extreme caution in resuming immunotherapy in patients with life-threatening irAE such as myocarditis.
In our case, the rechallenge with nivolumab has been well tolerated so far.
