Recombinant interleukin‐2 in patients aged younger than 60 years with acute myeloid leukemia in first complete remission: Results from Cancer and Leukemia Group B 19808

Abstract

BACKGROUND Recombinant interleukin-2 (rIL-2) induces cellular cytotoxicity against leukemia blasts. Patients with acute myeloid leukemia (AML) in first complete remission (CR) may harbor minimal residual disease that is susceptible to rIL-2–activated effector cells. METHODS In the Cancer and Leukemia Group B (CALGB) 19808 study, patients with AML in first CR were randomly assigned after all planned chemotherapy to receive a 90-day course of subcutaneously administered rIL-2 or no further therapy. The primary objective was to compare disease-free survival (DFS) between the 2 treatment arms. A total of 534 patients achieved a CR, 214 of whom were randomized. Six courses of low-dose daily rIL-2 were given for the expansion of cytotoxic effector cells, each followed by 3-day high-dose boluses given to trigger cytotoxicity against minimal residual disease. RESULTS On the protocol-specified intention-to-treat analysis, the hazards ratio for DFS was 0.75 (95% confidence interval, 0.52–1.09; P =.13); the 5-year DFS rate was 42% in the observation arm and 53% in the rIL-2 treatment arm. The hazards ratio for overall survival (OS) was 0.88 (95% confidence interval, 0.54–1.23; P =.34); the 5-year OS rate was 58% for the observation arm and 63% for the rIL-2 treatment arm. Twenty-five of the 107 patients randomized to treatment with rIL-2 either refused or were unable to initiate therapy and 30 patients did not complete their assigned therapy. However, significant toxicities were not commonly observed. The trial design did not anticipate the difficulties patients would encounter with protocol compliance. CONCLUSIONS The efficacy of immunotherapy with rIL-2 administered after intensive postremission treatment was not assessed as planned because of unexpected refusals by patients and/or their physicians to comply with protocol-directed therapy. Neither DFS nor OS was found to be significantly improved.

Maintenance therapy with decitabine in younger adults with acute myeloid leukemia in first remission: a phase 2 Cancer and Leukemia Group B Study (CALGB 10503)

“…Investigational use of drugs with alternative mechanisms of action remains of interest, but results have been disappointing with agents such as gemtuzumab ozogamicin 28,29 or, more recently, rIL-2 with or without histamine dihydrochloride. 16,30–36 One study with rIL-2/histamine dihydrochloride showed a statistically significant DFS benefit but no benefit for OS; 35 however, a recent meta-analysis, plus a subsequent report of a randomized trial from the Alliance, further dampen enthusiasm for use of rIL-2 in remission maintenance in AML. 16,36 …”

“…16,30–36 One study with rIL-2/histamine dihydrochloride showed a statistically significant DFS benefit but no benefit for OS; 35 however, a recent meta-analysis, plus a subsequent report of a randomized trial from the Alliance, further dampen enthusiasm for use of rIL-2 in remission maintenance in AML. 16,36 …”

“…16 † P -value is from Fisher’s exact test (not including unknowns).‡The patients were categorized according to the European LeukemiaNet (ELN) classification 25 as follows: Favorable Genetic Group included patients with t(8;21) or inv(16)/t(16;16) and cytogenetically normal AML (CN-AML) patients who harbored mutated CEBPA and/or mutated NPM1 without FLT3 -ITD; Intermediate-I Group included the remaining CN-AML patients who had wild-type CEBPA and mutated NPM1 with FLT3 -ITD or wild-type NPM1 with or without FLT3 -ITD; Intermediate-II Group included patients with t(9;11) and those with all other chromosome abnormalities that were not classified as Favorable or Adverse; and Adverse Group included patients with inv(3)/t(3;3), t(6;9), t(v;11)(v;q23), −5 or del(5q), −7, abn(17p) and complex karyotype with ≥3 abnormalities.…”

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia

“…The anti-leukemic activity of allogeneic HSCT relies not only on the effects of high dose chemotherapy or irradiation given during the conditioning regimen, but also on the immune-mediated graft-versus-leukemia effect [147–149]. The use of cytokines or pharmacologic agents to restore immune cell effector functions and, by extension, anti-leukemic effects represent other immunotherapeutic approaches that have been used in leukemia treatment [150–153]. …”

Epigenetics Territory and Cancer

“…On the contrary, the GG genotype and the G allele of the same polymorphism of IL-2 (rs2069762) are associated with higher risk of childhood lymphoma (Song et al 2012) as well as gastric cardia cancer (Wu et al 2009). There are also several reports on cancer immunotherapy with IL-2 in diverse types of cancers (Antony and Dudek 2010; Kolitz et al 2014;Guma et al 2014).…”