Immune dysregulation and alteration of the bone marrow microenvironment allowing plasma cells to escape immune surveillance are well-known factors associated with the proliferation of clonal plasma cells and development of multiple myeloma (MM). Whilst immunotherapeutic approaches are now commonplace in a wide spectrum of malignancies, this aberration of myeloma development gives rise to the biological rationale for the use of immune checkpoint inhibitors (ICIs) in MM. However, the initial experience with these agents has been challenging with limited single agent efficacy, significant toxicity, and side effects. Herein, we review the biological and immunological aspects of MM and ICIs. We discuss the basic biology of immune checkpoint inhibitors, mechanisms of resistance, and drug failure patterns, review the published clinical trial data for ICIs in MM, and look towards the future of ICIs for MM treatment.

Background: PARP (poly(ADP-ribose) polymerase) inhibitors are used more frequently in platinum-sensitive recurrent ovarian cancer. Methods: We conducted a meta-analysis to check the strength of evidence on the use of PARP inhibitors for relapsed platinum-sensitive ovarian tumors. Results: A total of 4 randomized controlled trials were included in our analysis with a total of 1,264 patients (PARP n = 780). Progression-free survival (PFS) was significantly better in the PARP group in BRCA-positive patients (hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.19-0.30; p < 0.00001). PFS was significantly better in the PARP group in BRCA-negative patients (HR 0.52, 95% CI 0.36-0.75; p < 0.00001). Similarly, we found a significant difference in overall survival (OS) between the two groups in BRCA-positive patients (HR 0.72, 95% CI 0.53-0.97, p= 0.03). Conclusion: PARP inhibitors in addition to standard platinum-based regimens along with subsequent maintenance therapy significantly improves PFS and OS with an acceptable side-effect profile in BRCA-positive women with recurrent, previously platinum-sensitive HGSOC.

Background. We performed meta-analysis to gather more evidence regarding clinical-molecular subgroups associated with better overall survival (OS) in advanced melanoma treated with checkpoint inhibitors. Materials and Methods. We performed a systematic search of PubMed, Scopus, Cochrane Library, and clinical trial.gov. Randomized clinical trials that compared a checkpoint inhibitor (nivolumab or pembrolizumab) with investigator choice chemotherapy or ipilimumab were included in our study. Hazard ratios (HR) and confidence interval (CI) were calculated for progression-free survival (PFS) and OS for each subgroup using generic inverse model along with the random effect method. Results. A total of 6 clinical trials were eligible for the meta-analysis. OS was prolonged in wild BRAF subgroup (HR 0.65, 95% CI 0.49-0.85, p 0.002), Programmed cell death subgroup (PD-1+) (HR 0.57, 95% CI 0.41-0.80, p 0.001), and high lactate dehydrogenase (LDH) level subgroup (HR 0.60, 95% CI 0.38-0.95, p 0.03). Similarly, we found increased OS in eastern cooperative oncology group (ECOG) 1, males and age >65 years subgroups. Conclusions. Checkpoint inhibitors significantly increased OS in patients with wild BRAF, positive PD-1, and high LDH. However, results should be interpreted keeping in mind associated significant heterogeneity. The results of this study should help in designing future clinical trials.

Pancreatic cancer carries poor prognosis. Establishing the diagnosis early could help in improving outcome. We are presenting a case of pancreatic cancer with delayed diagnosis. Our 60-year-old patient underwent multiple endoscopic ultrasound-guided biopsies with no evidence of malignancy. He had normal molecular tumor biomarkers. The patient needed 8 months to receive the diagnosis and initiate the treatment. There are no specific guidelines regarding choice of tissue sampling modalities in such cases.

Immunotherapy has become the standard of care for advanced and resectable lung cancer, and specific mutations may predict immunotherapy response. For example, STK11 mutations, which are more common in African American patients, are associated with immunotherapy resistance. A 68-year-old African American man with stage IIIB lung adenocarcinoma with mediastinal lymph node involvement progressed on first-line concurrent carboplatin-based chemoradiotherapy. Molecular testing of the patient’s subcarinal lymph node tissue revealed STK11 S216F, TP53 R273L, and RB1 splice site mutations; high tumor mutation burden (19.0 mutations/Mb); and high PD-L1 22c3 expression (TPS 70%, 2+ intensity). Treatment with carboplatin-based chemotherapy with radiation therapy failed to control the disease, but the patient has tolerated and responded well to intravenous pembrolizumab. Although STK11 mutations are associated with immunotherapy resistance, our patient demonstrated an exceptional and sustained response to immunotherapy for over two years. The patient’s STK11/TP53 co-mutation, along with high TMB and PD-L1 22c3 TPS scores, may help explain his continued responsiveness to immunotherapy and longer survival. Importantly, incorporating genetic ancestry differences in mutation prevalence and the impact of specific mutations and co-mutations, may help ensure the equitable and optimal treatment of all patients with lung cancers.