(1) Many of the significant advances in cancer management in recent years have centered on the development and introduction of molecularly targeted therapies, such as monoclonal antibodies and tyrosine kinase inhibitors.(2) Despite targeted therapy that has clearly benefited and even cured certain patients (eg, imatinib, trastuzumab), the ultimate goal of curing cancer, and the more immediate goal of replacing non-targeted chemotherapies with less toxic, targeted agents has yet to be achieved for most cancer patients.(3) Based on a systematic review of randomized controlled trials, examples of significant benefits in selected cancers are provided:(a) Non-Hodgkin's lymphoma (NHL) - A large meta-analysis and several individual randomised, controlled trials (RCTs) report that rituximab plus chemotherapy has a major survival advantage over chemotherapy alone in patients with NHL; an overview of six clinical trials supports the survival benefit of rituximab plus chemotherapy.(b) Renal cell carcinoma (RCC) - Temsirolimus or sunitinib has a significant survival benefit relative to interferon-alpha, and sorafenib carries such a benefit in patients resistant to standard therapy.(c) Colorectal cancer (CRC) - An overview of three RCTs in metastatic CRC revealed that bevacizumab plus 5-fluorouracil/leucovorin possesses a significant survival advantage over 5-fluorouracil/leucovorin and irinotecan/5-fluorouracil/leucovorin.(d) Non-small-cell lung cancer (NSCLC) - In refractory NSCLC, erlotinib significantly prolongs survival, particularly in nonsmokers, and gefitinib may have some utility in patients of Asian ethnicity.(e) Head and neck squamous-cell carcinoma (HNSCC) - Cetuximab plus radiotherapy (versus radiotherapy alone) significantly improves locoregional control and survival (hazard ratio [HR] 0.68; p = 0.005) without worsening radiotherapy-related toxicity.

Introducción: la artritis reumatoidea (AR) y los tratamientos indicados para su manejo pueden afectar la respuesta a la vacuna para SARS-CoV-2. Sin embargo, aún no se cuenta con datos locales. Objetivos: evaluar la respuesta humoral de la vacuna para SARS-CoV-2 y su seguridad en esta población. Materiales y métodos: estudio observacional. Se incluyeron pacientes ≥18 años, con AR ACR/EULAR 2010 que recibieron la vacunación para SARS-CoV-2. Detección de IgG anti-proteína S (kit COVIDAR). Resultados: se incluyeron 120 pacientes con AR. El 24,4% recibió tratamiento con glucocorticoides, 50,9% drogas biológicas y 13,3% inhibidores de JAK (janus kinases). El 6% había tenido infección por SARS-CoV-2 previamente. La vacuna más utilizada en la primera dosis fue Sputnik V (52,9%). El 25% recibió esquemas heterólogos. Luego de la primera dosis, el 59% presentó una prueba no reactiva o indeterminada, y un 18% luego de la segunda dosis. La aplicación de esquemas homólogos de vacuna Sinopharm (63,6% vs 13,3%, p<0,0001), y el uso de abatacept (27,3% vs 5,1%, p=0,005) y rituximab (18,2% vs 0%, p=0,001) al momento de la vacunación se asociaron a un resultado no reactivo o indeterminado. Conclusiones: similar a lo reportado en otras poblaciones internacionales, en esta cohorte, dos de cada 10 pacientes no desarrollaron anticuerpos. Una menor respuesta se asoció con la vacuna Sinopharm y al tratamiento con abatacept y rituximab.

Non-Hodgkin's lymphomas (NHL) are a heterogeneous group of lymphoproliferative disorders originating in B lymphocytes, T lymphocytes, or natural killer cells. Mantle cell lymphoma (MCL) accounts for approximately 6% of all newly diagnosed NHL cases. Radiation therapy with or without systemic therapy is a reasonable approach for the few patients who present with early-stage disease. Rituximab-based chemoimmunotherapy followed by high-dose therapy and autologous stem cell rescue (HDT/ASCR) is recommended for patients presenting with advanced-stage disease. Induction therapy followed by rituximab maintenance may provide extended disease control for those who are not candidates for HDT/ASCR. Ibrutinib, a Bruton tyrosine kinase inhibitor, was recently approved for the treatment of relapsed or refractory disease. This manuscript discusses the recommendations outlined in the NCCN Guidelines for NHL regarding the diagnosis and management of patients with MCL.

Standard treatment of transplant-eligible patients with relapsed diffuse large B-cell lymphoma (DLBCL) consists of rituximab and platinum-based chemotherapy, either ifosfamide, carboplatin, and etoposide (ICE) or dexamethasone, cytarabine, and cisplatin (DHAP), with autologous transplant consolidation for those with chemosensitive disease. Nonetheless, outcomes are suboptimal for patients failing rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). We performed a multi-center phase II trial investigating the safety and efficacy of ofatumumab, a monoclonal antibody against CD20, combined with ICE or DHAP second-line therapy in patients with relapsed or refractory DLBCL, grade 3b follicular lymphoma, or transformed follicular lymphoma. Sixty-one patients were treated with either ofatumumab-ICE (35) or ofatumumab-DHAP (26). The overall response rate (ORR) was 61%, and the complete response (CR) rate was 37%. In patients with 2 or 3 adverse risk factors according to the second-line, age-adjusted, international prognostic index, the ORR was 59% and CR 31%, and in patients with early-relapsing or primary refractory disease, the ORR was 55% and CR 30%. Toxicity was largely hematologic, and stem cell mobilization was successful in 43 of 45 patients. Substitution of ofatumumab for rituximab in standard second-line regimens following failure of R-CHOP is a promising approach. This trial was registered at www.clinicaltrials.gov as NCT00823719.

Approximately 10-25 % of patients with diffuse large B cell lymphoma (DLBCL) at the time of diagnosis exhibit bone marrow involvement (BMI). After introduction of rituximab, immunohistochemistry (IHC) markers lost to prognostic value in DLBCL patients. However, the specimens used have mainly been diagnostic tissues, not bone marrow (BM). It would thus be useful to determine the prognostic value of specific IHC markers of pathologic BM in DLBCL patients with BMI in the rituximab era. In the present study, a total of 580 DLBCL patients were analyzed 67 of whom had BMI. CD10, Bcl-6, MUM-1, Bcl-6 and Ki-67 dyeing on pathologic BM were applied. Bcl-2 positivity was more frequent in discordant BMI (P = 0.039) and high Ki-67 expression was more frequent in concordant BMI (P = 0.016). High Ki-67 expression independently predicted poor prognosis between the negative BMI group and each of the following BMI-positive groups: entire BMI (PFS, P < 0.001; OS, P < 0.001), concordant BMI (PFS, P = 0.024; OS, P = 0.007), and discordant BMI (PFS, P = 0.033; OS, P = 0.026). We found that Ki-67 expression in pathologic BM is a novel significant prognostic parameter of worse prognosis in DLBCL patients with BMI in the rituximab era.

BACKGROUND:

The use of biologic agents has revolutionized the treatment of rheumatoid arthritis (RA). However, there is much uncertainty about whether any agent may be preferable.

PURPOSE:

The aim of the study was to evaluate the comparative efficacy of biologic agents with a disease-modifying antirheumatic drug (DMARD) in RA patients without prior exposure to a DMARD, that is, DMARD naive.

METHODS:

MEDLINE, Cochrane, and Clinicaltrials.gov were searched from 1990 to August 2013 for randomized controlled trials comparing biologic agents in conjunction with a DMARD and DMARDs alone in DMARD (methotrexate [MTX])-naive RA patients. Information on patient characteristics, disease duration, and the American College of Rheumatology (ACR) 20/50/70/90 response rates after 52 weeks was extracted.

RESULTS:

Six randomized controlled trials totaling 9 study arms fulfilled the inclusion criteria. Data were analyzed by direct and indirect pairwise comparisons of 2 drugs against a common comparator. In the direct comparison, all 6 biologic therapies were associated with significantly higher likelihood of achieving an ACR20 compared with MTX alone (mean ORs, 1.43-2.99). For ACR50 and ACR70, all biologic agents except golimumab showed statistically significant mean ORs of 1.31 to 2.52 (ACR20) and 1.79 to 2.59 (ACR50). At ACR90, abatacept 10 mg/kg, adalimumab 40 mg, and rituximab 500 and 1000 mg were significantly better compared with MTX (mean ORs 1.92-2.89). The indirect comparison for ACR20 showed etanercept 50 mg significantly favored against adalimumab 40 mg (OR, 1.05-3.34), golimumab 50 mg (OR, 1.16-4.07), infliximab 3 mg/kg (OR, 1.21-3.61), and infliximab 6 mg/kg (OR, 1.02-3.06). At ACR50, etanercept 50 mg and rituximab 1000 mg showed significantly higher ORs compared with golimumab 100 mg at ORs 1.06 to 3.42 and ORs 1.07 to 3.42, respectively. No significant differences were observed in the biologic agents for indirect pairwise comparisons at ACR70 and ACR90.Lack of head-to-head clinical trial data directly comparing biologic agents makes indirect meta-analysis the only substitute. Safety and cost of these agents were not evaluated. Only a small number of trials could be evaluated because of the strict inclusion criteria required for an indirect meta-analysis. Unmeasured confounders could contribute to trial heterogeneity. The data on golimumab were difficult to reconcile with the other trials because of methodological differences.

CONCLUSIONS:

Overall, biological agents in conjunction with a DMARD performed similarly in the settings evaluated. However, there were some statistically significant differences. Etanercept 50 mg appears superior to adalimumab 40 mg, golimumab 50 mg, and infliximab 3 and 6 mg/kg at ACR20. Rituximab 1000 mg and etanercept 50 mg appeared superior to golimumab 100 mg at ACR50 in DMARD-naive patients. No agent was superior to all others at each ACR level.

OBJECTIVE:

Nonsevere relapses are more common than severe relapses in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but their clinical course and treatment outcomes remain largely unexamined. We undertook this study to analyze the outcomes of patients with nonsevere relapses in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial who were treated with prednisone according to a prespecified protocol.

METHODS:

RAVE was a randomized, double-blind, placebo-controlled trial comparing rituximab (RTX) to cyclophosphamide (CYC) followed by azathioprine (AZA) for induction of remission. Patients who experienced nonsevere relapses between months 1 and 18 were treated with a prednisone increase without a concomitant change in their nonglucocorticoid immunosuppressants, followed by a taper.

RESULTS:

Forty-four patients with a first nonsevere relapse were analyzed. In comparison to the 71 patients who maintained relapse-free remission over 18 months, these patients were more likely to have proteinase 3-ANCAs, diagnoses of granulomatosis with polyangiitis (Wegener's), and a history of relapsing disease at baseline. A prednisone increase led to remission in 35 patients (80%). However, only 13 patients (30%) were able to maintain second remissions through the followup period (mean 12.5 months); 31 patients (70%) had a second disease relapse, 14 of them with severe disease. The mean time to second relapse was 9.4 months (4.7 months in the group treated with RTX versus 13.7 months in the group treated with CYC/AZA; P < 0.01). Patients who experienced nonsevere relapses received more glucocorticoids than those who maintained remission (6.7 grams versus 3.8 grams; P < 0.01).

CONCLUSION:

Treatment of nonsevere relapses in AAV with an increase in glucocorticoids is effective in restoring temporary remission in the majority of patients, but recurrent relapses within a relatively short interval remain common. Alternative treatment approaches are needed for this important subset of patients.

BACKGROUND:

Biologic treatments for cancer continue to place a significant economic burden on healthcare stakeholders. Biosimilar therapies may help reduce this burden through cost savings, thereby increasing patient access.

OBJECTIVES:

The purpose of this study was to collate all published data to assess the weight of available evidence (quantity and quality) for proposed monoclonal antibody biosimilars and intended copies, for the treatment of cancer.

METHODS:

MEDLINE(®), Embase(®), and ISI Web of Science(®) databases were searched to September 2015. Conference proceedings (17) were searched (2012 to July 2015). Searches of the United States National Library of Medicine ClinicalTrials.gov registry were also conducted. Risk of bias assessments were undertaken to assess data strength and validity.

RESULTS:

Proposed biosimilars were identified in 23 studies (36 publications) in oncology and ten studies in 14 publications in oncology and chronic inflammatory diseases for bevacizumab, rituximab, and trastuzumab originators. Based on our review of the included published studies, and as inferred from the conclusions of study authors, the identified proposed biosimilars exhibit close similarity to their originators. Published data were also retrieved on intended copies of rituximab. It remains unclear what role these agents may have, as publications on rigorous clinical studies are lacking for these molecules.

CONCLUSION:

While biosimilar products have the potential to improve patient access to important biologic therapies, robust evidence of outcomes for monoclonal antibody biosimilars in treating cancer patients, including data from comparative efficacy and safety trials, is not yet available in the published literature. Significant data gaps exist, particularly for intended copies, which reinforces the need to maintain a clear differentiation between these molecules and true biosimilars. As more biosimilars become available for use, it will be important for stakeholders to understand fully the robustness of overall evidence used to demonstrate biosimilarity and gain regulatory approval.

BACKGROUND:

Primary cutaneous B-cell lymphoma (PCBCL) is a heterogeneous group of rare clonal B-cell lymphoproliferative disorders with distinct clinicopathologic features from more common nodal B-cell lymphomas.

METHODS:

We performed a systematic review of the relevant literature in the MEDLINE database and analyzed laboratory and clinical data. This review discusses the three most common types of

PCBCL:

primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle-center lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT).

RESULTS:

Skin biopsies with histology, immunohistochemistry, and molecular clonality studies are essential for a correct diagnosis of cutaneous B-cell lymphoma. Comprehensive lymphoma staging with laboratory and imaging studies and bone marrow aspiration and biopsy are important for determining the prognosis and differentiation of PCBCL from secondary skin involvement with systemic B-cell lymphomas. PCMZL and PCFCL are low-grade PCBCLs, with an estimated 5-year disease-specific survival rate of greater than 95%. Surgical excision or focal radiation therapy is sufficient to control stages T1 and T2 disease. Rituximab monotherapy is frequently used for patients with stage T3 disease. PCDLBCL, LT is an intermediate-grade B-cell lymphoma, with a 5-year disease-specific survival rate of approximately 50%. An anthracycline-based chemotherapy regimen with rituximab is usually required as initial therapy to improve outcomes.

CONCLUSIONS:

In less than a decade, significant progress has been made in our understanding of PCBCL. Novel classification, staging, and prognostic systems have resulted in more accurate diagnosis and prognosis. Although no randomized prospective studies have been conducted in PCBCL, therapies derived from systemic B-cell lymphomas have shown promising results.

BACKGROUND:

Pemphigus vulgaris (PV) is a blistering autoimmune bullous disease that is usually fatal without proper treatment. There are no clear treatment guidelines for PV at this time.

PURPOSE:

We suggest a standard treatment regimen for patients with PV based on the success of our treatment.

METHODS:

A retrospective chart review of 18 patients with PV was conducted to assess response to a similar approach using mycophenolate mofetil (MMF) and prednisone. Diagnosis was confirmed through routine histology, direct immunofluorescence, and indirect immunofluorescence, and patients were followed up for a total average of 35.2 months.

RESULTS:

We achieved complete disease control in 89% of patients using our treatment algorithm. Fourteen of 18 patients achieved complete disease control on therapy with prednisone and MMF. Three of the 4 patients who did not achieve control on MMF and prednisone went on to receive rituximab therapy, and two of those patients achieved disease control on rituximab. The average length of time from initiating therapy to 75% clearance of lesions was 4.5 months. Three of 18 patients were able to discontinue therapy after an average of 3 years and have remained in complete remission for more than 1 year.

LIMITATIONS:

This was a retrospective chart review with a small patient sample size.

CONCLUSIONS:

The combination therapy of MMF and prednisone is an effective treatment regimen to achieve rapid and complete control of PV. For those patients who fail treatment with MMF and prednisone, rituximab is an efficacious alternative therapy.