Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV.

The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874

Younger patients with chronic myeloid leukemia do well in spite of poor prognostic indicators: results from the randomized CML study IV.

Since the advent of tyrosine kinase inhibitors, the impact of age on outcome of chronic myeloid leukemia (CML) patients has changed. We therefore analyzed patients from the randomized CML study IV to investigate disease manifestations and outcome in different age groups. One thousand five hundred twenty-four patients with BCR-ABL-positive chronic phase CML were divided into four age groups: (1) 16-29 years, n = 120; (2) 30-44 years, n = 383; (3) 45-59 years, n = 495; and (4) ≥60 years, n = 526. Group 1 (adolescents and young adults (AYAs)) presented with more aggressive disease features (larger spleen size, more frequent symptoms of organomegaly, higher white blood count, higher percentage of peripheral blasts and lower hemoglobin levels) than the other age groups. In addition, a higher rate of patients with BCR-ABL transcript levels >10 % on the international scale (IS) at 3 months was observed. After a median observation time of 67.5 months, no inferior survival and no differences in cytogenetic and molecular remissions or progression rates were observed. We conclude that AYAs show more aggressive features and poor prognostic indicators possibly indicating differences in disease biology. This, however, does not affect outcome.

Assessment and Evaluation of Psychosocial Distress in Outpatients with Cancer at a University Hospital in Germany.

INTRODUCTION: Cancer patients (pts) suffer from a significant amount of psychosocial distress related to tumor disease itself or straining treatments. Despite recommendations on how to screen for and to deal with psychosocial distress in cancer pts, data about implementation of psycho-oncological interventions (poi) in outpatient settings of cancer pts are scarce. The aim of this study was to identify outpatients with cancer in need of poi and to evaluate different assessment instruments. METHODS: N = 200 outpatients with hemat-/oncological malignancies were interviewed between October 2015 and December 2017 at the University Hospital Mannheim using the Basic Documentation for Psycho-Oncology (PO-Bado) and the Hornheider Screening Instrument (HSI) - both clinician-administered assessment tools - followed by descriptive, univariate, and agreement analysis. RESULTS: N = 61 cancer pts (31%) were identified to be in need for poi considering the results of both questionnaires. The number of identified pts in need of poi was lower when analyzing the results of the PO-Bado (n = 42, 21%) and the HSI (n = 39, 20%) separately. The degree of agreement between the results of PO-Bado and HSI was low (kappa = 0.3655). Several factors like gender, age and diagnosis were identified to have significant impact on the need for poi (p ≤ 0.05). CONCLUSION: Our study underlines that different screening instruments for psychosocial distress may identify disparate populations of cancer pts. The study data also revealed significant characteristics that might be associated with elevated levels of psychosocial distress and a clear indication for poi. However, further analyses on larger populations of cancer pts are needed to provide information how to transfer positive screening to poi in clinical routine.

Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV.

PURPOSE: Deep molecular response (MR(4.5)) defines a subgroup of patients with chronic myeloid leukemia (CML) who may stay in unmaintained remission after treatment discontinuation. It is unclear how many patients achieve MR(4.5) under different treatment modalities and whether MR(4.5) predicts survival. PATIENTS AND METHODS: Patients from the randomized CML-Study IV were analyzed for confirmed MR(4.5) which was defined as ≥ 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction in two consecutive analyses. Landmark analyses were performed to assess the impact of MR(4.5) on survival. RESULTS: Of 1,551 randomly assigned patients, 1,524 were assessable. After a median observation time of 67.5 months, 5-year overall survival (OS) was 90%, 5-year progression-free-survival was 87.5%, and 8-year OS was 86%. The cumulative incidence of MR(4.5) after 9 years was 70% (median, 4.9 years); confirmed MR(4.5) was 54%. MR(4.5) was reached more quickly with optimized high-dose imatinib than with imatinib 400 mg/day (P = .016). Independent of treatment approach, confirmed MR(4.5) at 4 years predicted significantly higher survival probabilities than 0.1% to 1% IS, which corresponds to complete cytogenetic remission (8-year OS, 92% v 83%; P = .047). High-dose imatinib and early major molecular remission predicted MR(4.5). No patient with confirmed MR(4.5) has experienced progression. CONCLUSION: MR(4.5) is a new molecular predictor of long-term outcome, is reached by a majority of patients treated with imatinib, and is achieved more quickly with optimized high-dose imatinib, which may provide an improved therapeutic basis for treatment discontinuation in CML.