Attenuated cytarabine, etoposide, dexamethasone plus rituximab (R-Mini-CYVE) regimen for patients with relapsed or refractory B-cell non-Hodgkin's lymphoma not eligible for intensive chemotherapy.

OBJECTIVES: To evaluate the efficacy and tolerability of an attenuated immunochemotherapy regimen based on cytarabine, etoposide and dexamethasone plus rituximab (R-mini-CYVE) in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). METHODS: We included pretreated adult patients with B-cell NHL who were ineligible for high-dose immunochemotherapy (HDT). Cytarabine and etoposide were given at four different dose levels, depending on the patient's frailty. Up to 8 cycles were administered. RESULTS: Between 2013 and 2019, 56 patients with diffuse large B-cell lymphoma (n = 45, 80%) and indolent B-cell lymphoma (n = 11, 20%) were included. Median age was 75 (range: 36-88). Nineteen patients (35%) had a performance status ≥2. Patients received a median of 4 cycles of R-mini-CYVE. The objective response and the complete response rates were 50% and 33%, respectively. Median progression-free survival and overall survival times were 5.7 (95% CI: 0.5-10.9) and 14.7 (95% CI: 3.5-25.9) months, respectively. Grade ≥3 anaemia, thrombocytopenia and neutropenia occurred in 44%, 55% and 60% of the patients, respectively. The most frequent non-haematological grade ≥3 adverse events were sepsis (21%), fatigue (13%) and cytarabine-related neurotoxicity (5%). CONCLUSION: R-mini-CYVE demonstrated a meaningful antitumour efficacy and an acceptable safety profile in patients with relapsed/refractory B-cell NHL who were ineligible for HDT.

Should we screen patients with hematologic malignancies for COVID-19?

The coronavirus disease (COVID-19) pandemic has posed several challenges to the hematology community to re-organize the medical care of patients with hematologic malignancies. Whereas the oncology societies favored a more or less conservative approach which considered the possibility of delaying treatment administration on a case-by-case basis, the hematology community guidelines were less stringent and recommended adequate individualized regimens. As countries are de-escalating the lockdown and the medical community is unable to foresee the end of the current outbreak will and whether the pandemic would eventually come back as a seasonal infection, there is interest in screening of patients with hematology malignancies with COVID-19 instead of limiting access to curative treatments. The rapidly accumulating knowledge about COVID-19 allows a better understanding of the diagnostic tools that may be potentially used in screening. Herein, we briefly review the pathophysiology of COVID-19, the rationale of screening of patients with hematologic malignancies, tools for screening, and available guidelines.

The management of patients with metastatic prostate cancer during the COVID-19 pandemic.

During the ongoing global pandemic of coronavirus disease 2019 (COVID-19), the benefit of treating patients with cancer must be weighed against the COVID-19 infection risks to patients, staff and society. Prostate cancer is one of the most common cancers among men and raises particular interest during the pandemic as recent reports show that the TMPRSS2 (and other serine proteases), which facilitate the entry, replication and budding of the virion from a cell, can be inhibited using androgen deprivation therapy. Nevertheless, patients with metastatic prostate cancer commonly receive chemotherapy which may compromise their immune system. This paper aims to address the current status of the COVID-19 in patients with cancer overall and suggests an optimal approach to patients with metastatic prostate cancer.

Surgical outcome of biopsy-proven lobular neoplasia: is there any difference between lobular carcinoma in situ and atypical lobular hyperplasia?

OBJECTIVE: The aims of our study were to determine the frequency of malignancy after surgical excision of biopsy-proven lobular carcinoma in situ (LCIS) or atypical lobular hyperplasia (ALH) lesions, to assess any difference between pure LCIS and pure ALH lesions regarding their radiologic presentation and the malignancy upgrade rate after surgical excision, and to evaluate the outcome of lesions that were not excised surgically but were followed up. MATERIALS AND METHODS: Radiologic and pathologic records of 14,435 imaging-guided needle biopsies of the breast performed between 2004 and 2008 in three different institutions were retrospectively reviewed. A total of 126 patients (0.9%) had biopsy-proven LCIS or ALH, or both, as the highest-risk lesion. Among the 126 patients, 89 (71%) continued to surgery, and 14 were followed up for more than 24 months. The Mantel-Haensel chi-square test was used for statistical analysis. RESULTS: Cancer upgrade was documented in 17 of the 43 LCIS (40%), 11 of the 40 ALH (27%), and two of the six combined ALH and LCIS lesions (33%) surgically excised, for a total malignancy upgrade rate of 34% (30/89). Both LCIS and ALH lesions presented mammographically in most cases as microcalcifications (p = 0.078). None of the 14 patients followed up for a mean period of 51 months showed development of malignancy. CONCLUSION: No statistically significant difference was found between mammographic presentation and postsurgical outcome of LCIS versus ALH lesions. Surgical excision of these lesions is recommended as long as no evident criteria are provided to differentiate those that might be associated with an underlying malignancy.

Dose escalation phase 1 study of radiotherapy in combination with anti-cytotoxic-T-lymphocyte-associated antigen 4 monoclonal antibody ipilimumab in patients with metastatic melanoma.

BACKGROUND: A synergy between radiotherapy and anti-cytotoxic-T-lymphocyte-associated antigen 4 (anti-CTLA-4) monoclonal antibody has been demonstrated preclinically. The Mel-Ipi-Rx phase 1 study aimed to determine the maximum tolerated dose (MTD) and safety profile of radiotherapy combined with ipilimumab in patients with metastatic melanoma. PATIENTS AND METHODS: A 3+3 dose escalation design was used with 9, 15, 18 and 24 Gy dose of radiotherapy at week 4 combined with 10 mg/kg ipilimumab every 3 weeks for four doses. Patients with evidence of clinical benefit at week 12 were eligible for maintenance with ipilimumab 10 mg/kg every 12 weeks starting at week 24 until severe toxicity or disease progression. The database lock occurred on April 30, 2019. Tumor growth rate of irradiated lesions and non-irradiated lesions were analyzed to assess the systemic immunologic antitumor response. Blood immune monitoring was performed before and during treatment to determine if radiotherapy could modify ipilimumab pharmacodynamics. RESULTS: 19 patients received ipilimumab between August 2011 and July 2015. Nine patients received the four doses of ipilimumab. All patients received the combined radiotherapy. Grade 3 adverse events occurred in nine patients, the most common being colitis and hepatitis. No drug-related death occurred. Dose limiting toxicity occurred in two of six patients in the cohort receiving 15 Gy. The MTD was 9 Gy. Two patients had complete response, three had partial response response and seven had stable disease, giving an objective response rate of 31% and a clinical benefit rate of 75% at week 24. The median duration of follow-up was 5.8 years (Q1=4.5; Q3=6.8). The median overall survival (95% CI) was estimated at 0.9 years (0.5-2). The median progression-free survival (PFS) (95% CI) was 0.4 (0.2-1.4). Radiotherapy combined with ipilimumab was associated with increased CD4+ and CD8+ICOS+ T cells. Increased CD8+ was significantly associated with PFS. CONCLUSION: When combined with ipilimumab at 10 mg/kg, the MTD of radiotherapy was 9 Gy. This combination of ipilimumab and radiotherapy appears to be associated with antitumor activity. Increased CD8+ was significantly associated with PFS. Thus, immune biomarkers may be useful for early response evaluation. TRIAL REGISTRATION NUMBER: NCT01557114.

The current state of immune checkpoint inhibitors in the first-line treatment of renal cancer.

Until recently, tyrosine kinase inhibitors (TKI) were the only approved drugs for the first-line treatment of metastatic renal cell carcinoma (mRCC). Emerging trials of immune checkpoint inhibitors (ICI)-based regimens have shown survival benefits over the standard TKI. These studies challenge a paradigm shift in the management of mRCC concerning the identification of the subgroup of patients that would benefit from ICI in treatment-naive mRCC, the possibility of treatment discontinuation between TKI and ICI, and the sequencing of surgery and systemic treatment. This paper reviews the currently available data and discusses the paradigm shift concerning first-line treatments of mRCC.