Current Information and Recommendations on the Discontinuation of TKI Inhibitors in Chronic Myeloid Leukemia

PURPOSE OF REVIEW: Discontinuation of tyrosine kinase inhibitors (TKIs) in chronic phase chronic myeloid leukemia (CP-CML) patients has become a reality. Treatment-free remission (TFR) is the term that identifies success after discontinuation. RECENT FINDINGS: Several trials have demonstrated that with imatinib about 40% of patients discontinuing treatment in deep and stable molecular response remain disease-free. Second-generation TKIs have improved the rate of deep molecular responses and allowed to increase the percentage of patients attempting treatment discontinuation. We hereby review the current information based on the available published data and discuss the current suggestions on how to move TFR into the clinical practice

Treatment with nilotinib after cytogenetic relapse at 12 months in a patient in chronic phase with sub-optimal response to imatinib

We report a case of patient with chronic myeloid leukemia who started imatinib at standard dose and obtained a sub-optimal response at 6 months. Considering the patient as a possible "late responder", we decided not to change the imatinib dose, but, at 12 months, we did not achieve a complete cytogenetic response. At that time, we decided to switch to a second-generation tyrosine kinase inhibitor (TKI), nilotinib 800 mg/day, obtaining soon a major molecular response. Recently, the retrospective application of European LeukemiaNet guidelines in large cohorts of patients suggested that patients whose response to imatinib is sub-optimal at 6 months showed significantly worse survival. Therefore we can hypothesise that this kind of patients could be eligible for an early switch to second-generation TKI

Nilotinib after resistance to imatinib in CML patients with Wolf-Parkinson White syndrome

We report a case of a young man affected by Wolf-Parkinson White syndrome, who was diagnosed as having chronic myeloid leukemia. He started imatinib at standard dose of 400 mg/day and he reached a partial cytogenetic response at 6 months, a sub-optimal response according to European LeukemiaNet criteria of 2006. For this reason he increased imatinib dose to 600 mg/day, but after 3 months he suddenly lost his hematologic response. Cytogenetic analysis performed at this time showed a cytogenetic relapse and acquisition of an additional cytogenetic abnormality (trisomy 8). Considering the patient as a failure at this time, he switched to second-generation tyrosine kinase inhibitor, nilotinib at the dose of 800 mg/day. He reached complete cytogenetic remission after 3 months and nilotinib was safely administered without further QTc prolongation

Cocaine abuse may influence the response to imatinib in CML patients.

To the Editor: Cocaine is a 2-beta-carbomethoxy-3beta-benzoxytropane, which effects local anesthetic action by blocking the initiation or conduction of nerve impulse [1][1]. Many drugs of abuse are substrates (amphetamines, codeine, nicotine) or inhibitors (cocaine) of polymorphic cytochrome p45

Sustained molecular remission after low dose gemtuzumab-ozogamicin in elderly patients with advanced acute promyelocytic leukemia.

We report here a preliminary experience with gemtuzumab ozogamicin (GO) used at low dosage (3 mg/m2) in 3 elderly patients with acute promyelocytic leukaemia (APL) who presented molecular relapse and were unfit for intensive chemotherapy

Current Strategies and Future Directions to Achieve Deep Molecular Response and Treatment-Free Remission in Chronic Myeloid Leukemia

The treatment of chronic myeloid leukemia (CML) has been radically changed by the approval of tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity. CML is now managed as a chronic disease requiring long-term treatment and close molecular monitoring. It has been shown that in a substantial number of patients who have achieved a stable deep molecular response (DMR), TKI treatment can be safely discontinued without loss of response. Therefore, treatment-free remission (TFR), through the achievement of a DMR, is increasingly regarded as a feasible treatment goal in many CML patients. However, only nilotinib has approval in this setting and a number of controversial aspects remain regarding treatment choices and timings, predictive factors, patient communication, and optimal strategies to achieve successful TFR. This narrative review aims to provide a comprehensive overview on how to optimize the path to DMR and TFR in patients with CML, and discusses recent data and future directions

Low Incidence Rate of Opportunistic and Viral Infections During Imatinib Treatment in Chronic Myeloid Leukemia Patients in Early and Late Chronic Phase.

<!--StartFragment--> <p class="MsoNormal" style="text-align: justify; line-height: 150%;"><span style="font-family: Arial; mso-ansi-language: EN-GB;" lang="EN-GB">Background: Imatinib has become first line therapy in chronic myeloid leukemia patients. Little is known about the infective consequences during the treatment with this drug in large series of chronic phase patients. </span></p> <p class="MsoNormal" style="text-align: justify; line-height: 150%;"><span style="font-family: Arial; mso-ansi-language: EN-GB;" lang="EN-GB">Material and methods: From January 2001 to September 2006 we treated with imatinib 250 patients in first line (early CP) or after interferon failure (late CP), out of clinical trials and recorded all the bacterial and viral infections occurred.</span></p> <p class="MsoNormal" style="text-align: justify; line-height: 150%;"><span style="font-family: Arial; mso-ansi-language: EN-GB;" lang="EN-GB">Results: We recorded a similar incidence of bacterial and viral infections both in first line and late CP patients (respectively, 16% and 13%) during 3.5 years of follow-up. Analysis of presenting features predisposing to infections revealed differences only in late CP patients, with elevated percentage of high Sokal risk patients and a more longer median time from diagnosis to start of imatinib.</span></p> <p class="MsoNormal" style="text-align: justify; line-height: 150%;"><span style="font-family: Arial; mso-ansi-language: EN-GB;" lang="EN-GB">Conclusions: Opportunistic infections and reactivation of Herpes Zoster are observed during imatinib therapy at very low incidence.</span></p> <!--EndFragment--&gt

A population-based study on myelodysplastic syndromes in the Lazio Region (Italy), medical miscoding and 11-year mortality follow-up. The Gruppo Romano-Laziale Mielodisplasie experience of retrospective multicentric registry

Data on Myelodysplastic Syndromes (MDS) are difficult to collect by cancer registries because of the lack of reporting and the use of different classifications of the disease. In the Lazio Region, data from patients with a confirmed diagnosis of MDS, treated by a hematology center, have been collected since 2002 by the Gruppo Romano-Laziale Mielodisplasie (GROM-L) registry, the second MDS registry existing in Italy. This study aimed at evaluating MDS medical miscoding during hospitalizations, and patients' survival. For these purposes, we selected 644 MDS patients enrolled in the GROM-L registry. This cohort was linked with two regional health information systems: the Hospital Information System (HIS) and the Mortality Information System (MIS) in the 2002-2012 period. Of the 442 patients who were hospitalized at least once during the study period, 92% had up to 12 hospitalizations. 28.5% of patients had no hospitalization episodes scored like MDS, code 238.7 of the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM). The rate of death during a median follow-up of 46 months (range 0.9-130) was 45.5%. Acute myeloid leukemia (AML) was the first cause of mortality, interestingly a relevant portion of deaths is due to cerebro-cardiovascular events and second tumors. This study highlights that MDS diagnosis and treatment, which require considerable healthcare resources, tend to be under-documented in the HIS archive. Thus we need to improve the HIS to better identify information on MDS hospitalizations and outcome. Moreover, we underline the importance of comorbidity in MDS patients' survival

Italian Physicians' Perceptions about the Role of Asciminib in Later Lines Chronic Myeloid Leukemia in Clinical Practice: A GIMEMA Survey

Unmet needs remain in later lines chronic myeloid leukemia (CML): the response rate and the overall survival of resistant patients in the chronic phase who changed a second-generation TKI in the second line with another TKI with similar action are usually poor, while the off-target toxicities and the potential development of mutations increase. The recent approval of asciminib, a STAMP inhibitor, in the third line, has the potential to soon change the therapeutic algorithm for this subset of patients. Here, we report the results of a GIMEMA survey assessing the number of patients currently treated in the third line in Italy, the current approach in later lines by Italian physicians, and the future role of this drug according to the reason to switch to asciminib (resistance and/or intolerance), as well as the perceptions about the future position of this agent

Case Report: Avelumab and ruxolitinib to manage polycythemia vera and secondary metastatic Merkel cell carcinoma: a possible successful combination

We describe a case of second primary malignancy in a 65-year-old patient affected by polycythemia vera treated with the JAK 1/2 inhibitor ruxolitinib. The latter is recognized as a risk factor for the onset of non-melanoma skin cancers in many retrospective and perspective studies, but the concomitant use of ruxolitinib with new immunotherapies is very rarely reported, and the safety of this association is still not clear. In our case, ruxolitinib combined with the anti-PD-L1 avelumab demonstrated both safety and efficacy for hematological disease control and underlying carcinoma remission