Prospective Observational Study Comparing Calcium and Sodium Levofolinate in Combination with 5-Fluorouracil in the FOLFIRI Regimen

Lessons Learned

• The use of sodium levofolinate (Na-Lev) is safe in combination with continuous infusion 5-fluorouracil in patients with gastrointestinal tumors treated with the FOLFIRI regimen.
• A comparison with calcium levofolinate (Ca-Lev) showed a similar toxicity profile. The advantages of Na-Lev over Ca-Lev might be the faster drug preparation and the shorter time of drug administration.

     

Antibiotics and Imiquimod for Cutaneous T-Cell Lymphoma in Veterans: A Patient Population with Agent Orange Exposure

Lessons Learned

• Staphylococcus aureus infection in cutaneous T-cell lymphoma (CTCL) is thought to contribute to disease progression; thus, adjunctive treatment with antibiotics warrants further investigation.
• This trial of antibiotic therapy followed by imiquimod in early stage CTCL was not completed because of difficulties with patient accrual.

     

Melatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma

Lessons Learned

• Melatonin did not increase the efficacy of systemic chemotherapy in melanoma.
• Metformin did not increase the efficacy of systemic chemotherapy in melanoma.

     

Cabozantinib and Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer

Lessons Learned

• Antitumor activity was observed in the study population.
• Dose modifications of cabozantinib improve long-term tolerability.
• Biomarkers are needed to identify patient populations most likely to benefit.
• Further study of cabozantinib with or without panitumumab in patients with metastatic colorectal cancer is warranted.

     

A Phase I Open-Label Clinical Trial Evaluating the Therapeutic Vaccine hVEGF26–104/RFASE in Patients with Advanced Solid Malignancies

Lessons Learned

• The novel therapeutic vaccine hVEGF_26–104/RFASE was found to be safe and well tolerated in patients with cancer.
• hVEGF_26–104/RFASE failed to induce seroconversion against native hVEGF₁₆₅ and, accordingly, neither a decrease in circulating vascular endothelial growth factor (VEGF) levels nor clinical benefit was observed.
• Remarkably, hVEGF_26–104/RFASE induced VEGF₁₆₅-neutralizing antibodies in a nonhuman primate model. The absence of seroconversion in human calls for caution in the interpretation of efficacy of human vaccines in nonhuman primates.

     

Adoptive Transfer of Autologous Invariant Natural Killer T Cells as Immunotherapy for Advanced Hepatocellular Carcinoma: A Phase I Clinical Trial

Lessons Learned

• Administration of autologous invariant natural killer T (iNKT) cells was safe and well-tolerated in patients with hepatocellular carcinoma (Barcelona Clinic Liver Cancer stage B/C).
• Expanded iNKT cells produced T-helper 1–like responses with possible antitumor activity.
• No severe adverse events were observed in any of the enrolled patients, including one patient who received 10¹⁰ in vitro–expanded autologous iNKT cells as a single infusion.

     

How Have Prognostic Factors Changed with Novel Therapies?

Chronic lymphocytic leukemia (CLL) is characterized by a heterogeneous clinical course. A subset of patients never require treatment, while others progress from early stages to symptomatic disease requiring treatment within a few years. To estimate the likelihood of disease progression and survival much effort has been devoted to the identification of prognostic markers.¹ In addition to the clinical staging systems developed by Rai and Binet, molecular and genetic markers have provided

Disclosures

The authors is named as an inventor on a US patent held by NIH on the use of ZAP70 as a prognostic marker in CLL and has received royalty payments. The author has received research support from Pharmacyclics, an AbbVie company, Acerta, a member of the Astra-Zeneca group, and Merck.

References

• 1.Sun C, Wiestner A. Prognosis and therapy of chronic lymphocytic leukemia and small lymphocytic lymphoma. Cancer Treat Res. 2015;165:147-175.
• 2.Kipps TJ, Stevenson FK, Wu CJ, et al. Chronic lymphocytic leukaemia. Nat Rev Dis Primers. 2017;3:16096.
• 3.Hallek M, Cheson BD, Catovsky D, et al. Guidelines for diagnosis, indications for treatment, response assessment and supportive management of chronic lymphocytic leukemia. Blood. 2018;131(25):2745-2760.
• 4.Bulian P, Shanafelt TD, Fegan C, et al. CD49d is the

     

Progress in Targeting the TGFβ Pathway

Signaling by the transforming growth factor-β (TGF-β) superfamily is important in the regulation of hematopoiesis and is dysregulated in myelodysplastic syndromes (MDS), contributing to ineffective hematopoiesis and clinical cytopenias. TGF-β, activins and growth differentiation factors exert inhibitory effects on red cell formation by activating canonical SMAD2/3 pathway signaling. SMAD2/3 overactivation is seen in numerous subtypes of MDS. Furthermore, reduced levels of inhibitory SMAD7 are

References

• 1.Valcarcel D, Verma A, Platzbecker U, et al. Phase 2 Study of Monotherapy Galunisertib (LY2157299 Monohydrate) in Very Low-, Low-, and Intermediate-Risk Patients with Myelodysplastic Syndromes. Blood. 2015;126:1669.
• 2.Suragani RN, Cawley SM, Li R, Wallner S, et al. Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine β-thalassemia. Blood. 2014 Jun 19;123(25):3864-72.
• 3.Dussiot M, Maciel TT, Fricot A, et al. Nat Med. 2014 Apr;20(4):398-407.
• 4.

     

Immune biomarkers of response to immunotherapy in patients with high-risk smoldering myeloma

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An Embryonic Diapause-like Adaptation with Suppressed Myc Activity Enables Tumor Treatment Persistence

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Targeting Tumors with IL-10 Prevents Dendritic Cell-Mediated CD8+ T Cell Apoptosis

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Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: Where do we stand?

Plain Language Summary

• Patients with colorectal cancer that has spread to the lining of the abdomen (peritoneum) benefit from surgery to remove all the cancer.
• The addition of certain types of intra-abdominal chemotherapy during surgery improves survival for select patients.

     

Binary pan-cancer classes with distinct vulnerabilities defined by pro- or anti-cancer YAP/TEAD activity

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Seroconversion rates following COVID-19 vaccination among patients with cancer

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Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma

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A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications

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Expanding control of the tumor cell cycle with a CDK2/4/6 inhibitor

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T cell immune deficiency rather than chromosome instability predisposes patients with short telomere syndromes to squamous cancers

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Immunogenicity of SARS-CoV-2 messenger RNA vaccines in patients with cancer

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Real World Treatment of Patients with Relapsed/Refractory Myeloma

Translating clinical trial results into robust treatment options remains an important issue for patients with relapsed/refractory multiple myeloma (RRMM). The availability of different treatment regimens in different countries, the heterogeneous patient population among clinical trials versus real-world data (i.e. the under-representation of frail patients or patients with severe renal impairment in several clinical trials) and the clinical practice setting contribute to discrepant results

Causes for Discrepancies between Clinical Trial and RW Data

The most easily identifiable factor for discrepancies between clinical trials and RW data is patient selection. Eligibility criteria delineate a study population that may be substantially different from the general RW population with RRMM. Thus, extrapolating the clinical trials results is cautious by principle.¹ Frail patients with comorbidities are usually excluded from clinical trials; however, they represent the most challenging patient group in clinical practice. Furthermore, the

RW Data in RRMM Patients

The prospective, non-interventional EMMOS study has revealed several approaches in the RW treatment of RRMM, depending on the treatment setting and the availability of novel agents. Bortezomib, thalidomide and lenalidomide remain important backbone regimens, whereas prior autologous transplantation improves outcomes in the subsequent lines of therapy.¹⁴ In the RW, RRMM patients present with an unmet need for a more effective therapeutic approach inducing deep and durable responses in the

Conclusion

RW data on the role of novel agents and their combinations among patients with RRMM have confirmed their contribution in the significant improvement in patient outcomes and the prolongation of survival. RW evidence is valuable, which is reflected on the conduction of large multicenter RW studies such as the EMMOS and the INSIGHT studies.^14,30 Clinical trial and RW data are complementary and they should be considered as important feedback to improve both the clinical trial designs and our

References

• 1.Sherman RE, Anderson SA, Dal Pan GJ, et al. Real-World Evidence - What Is It and What Can It Tell Us? N Engl J Med. 2016;375:2293-2297.
• 2.Combest AJ, Reitsma DJ, Moseley A, et al. Adult participation in oncology clinical trials by indication, race, and age. J. Clin. Oncol. 2013;31(15 suppl):e17586.
• 3.Myeloma, U. K. Myeloma Patient Experience Report 2016. Myeloma, UK, 2016.
• 4.Richardson PG, San Miguel JF, Moreau P, et al. Interpreting clinical trial data in multiple myeloma: translating findings to the