FDA approval of daratumumab for Multiple Myeloma

The Food and Drug Administration (FDA) announced their approval of daratumumab in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant.

“Today’s approval of DARZALEX (daratumumab) underscores the significant clinical benefit of this CD38 monoclonal antibody and our efforts to advance treatment paradigms to change the course of the disease,” said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC in a press release. “Importantly, this milestone also highlights the efficiency of the FDA’s Real-Time Oncology Review process, ensuring that proven treatment regimens, such as DARZALEX plus lenalidomide and dexamethasone, are made available to patients as soon as possible.”

The decision for approval was made based on results of MAIA, an open-label, randomized (1:1) phase III study comparing dartumumab (16 mg/kg) in combination with lenalidomide and low-dose dexamethasone (DRd) to lenalidomide and low-dose dexamethasone (Rd), in 737 patients.

The trial showed an improvement in progression-free survival (PFS) with DRd compared with Rd. The median PFS had not been reached in the DRd arm and was 31.9 months in the Rd arm (HR 0.56; 95% CI: 0.43, 0.73; p<0.0001). The median time to response was 1.05 months (range: 0.2 to 12.1 months) in the DRd group and 1.05 months (range: 0.3 to 15.3 months) in the Rd group. The median response duration had not been reached in the DRd group and was 34.7 months (95% CI: 30.8, not estimable) in the Rd group.

In the DRd arm, the most frequent (≥20%) adverse reactions were infusion reactions, diarrhea, constipation, nausea, peripheral edema, fatigue, back pain, asthenia, pyrexia, upper respiratory tract infection, bronchitis, pneumonia, decreased appetite, muscle spasms, peripheral sensory neuropathy, dyspnea and cough.

Daratumumab can cause severe and/or serious infusion reactions, including anaphylactic-related ones. Patients should be pre‑medicated with antihistamines, antipyretics and corticosteroids and frequently monitored during the entire infusion. The recommended daratumumab dose is 16 mg/kg actual body weight. 

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Source: https://www.cancernetwork.com/multiple-myeloma/fda-approves-daratumumab-combination-multiple-myeloma

Sickle Cell Disease and Voxelotor

According to results of phase 3 study, Voxelotor increased hemoglobin levels and reduced markers of hemolysis among sickle cell disease patients. Although two medications approved by the FDA are available (hydroxyurea and L-glutamine [Endari, Emmaus Life Sciences]), chronic medical complications and early death in persons with sickle cell disease remain a substantial burden. In particular, chronic organ dysfunction has become a leading cause of death in adults with sickle cell disease in the United States.

Voxelotor (GBT440, Global Blood Therapeutics) — a deoxygenated sickle hemoglobin polymerization inhibitor — reversibly binds with hemoglobin to help stabilize the oxygenated hemoglobin state. In a previous phase 1/phase 2 trial, voxelotor demonstrated favorable pharmacokinetics and dose-dependent increases in affinity of hemoglobin and oxygen with low-grade toxic effects.

For the current phase 3, international, multicenter, double-blind HOPE trial,  274 patients with sickle cell disease in a 1:1:1 ratio were assigned to receive once-daily voxelotor at a dose of 1,500 mg (n = 90; median age, 24 years; range, 12-59) or 900 mg (n = 92; median age, 24 years; range, 12-59), or placebo (n = 92; median age, 28 years; range, 12-64).

Most of the patients were black (n = 183) and 159 were female. A majority in each group had homozygous hemoglobin S and had experienced at least two vaso-occlusive crises within the past month. About two-thirds were receiving hydroxyurea.

The percentage of patients who demonstrated an increase in hemoglobin level of more than 1 g/dL at 24 weeks served as the study’s primary endpoint. Change in hemoglobin level from baseline to week 24, markers associated with hemolysis, and the incidence rate of vaso-occlusive crises served as secondary endpoints.

Median follow-up was 42.3 weeks (range, 0.1-73.3) in the 1,500-mg voxelotor group, 38.1 weeks (range, 4-72.4) in the 900-mg voxelotor group, and 37.2 weeks (range, 8.1-72.9) in the placebo arm.

Results of the intention-to-treat analysis showed hemoglobin response at 24 weeks among a significantly higher percentage of patients in the 1,500-mg voxelotor group (51%; 95% CI, 41-61) than the placebo group (7%; 95% CI, 1-12). One-third of patients (33%; 95% CI, 23-42) in the 900-mg voxelotor group responded to the treatment by week 24.

Researchers observed a higher percentage of responses among patients in the 1,500-mg voxelotor group than the placebo group regardless of concurrent hydroxyurea use or anemia severity at baseline.

Adjusted mean change in hemoglobin level from baseline to week 24 in the intention-to-treat analysis was 1.1 g/dL (95% CI, 0.9-1.4) in the 1,500-mg voxelotor group, 0.6 g/dL (95% CI, 0.3-0.8) in the 900-mg dose group and –0.1 g/dL (95% CI, –0.3 to 0.2) in the placebo group.

Fewer patients in the 1,500-mg and 900-mg groups experienced worsening anemia between baseline and 24 weeks than in the placebo group. Additionally, the 1,500-mg group demonstrated significantly greater reductions in indirect bilirubin levels and percentage of reticulocytes than the placebo group.

Grade 3 or higher adverse events occurred among 26% of patients in the 1,500-mg and placebo groups and 23% of patients in the 900-mg group. Investigators determined most adverse events were unrelated to treatment.

The absence of an increased incidence rate of vaso-occlusive crisis with voxelotor despite significant increases in the hemoglobin level suggests that voxelotor raises hemoglobin levels without negatively affecting blood viscosity. Longer-term follow-up is needed to further characterize the effect of voxelotor on the incidence of vaso-occlusive crisis.

The hemoglobin response and reduction in hemolysis observed with an orally administered, once-daily medication with side effects that minimally affect lifestyle may make voxelotor a promising advancement in the management of sickle cell disease if approved by the FDA.

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Source: HemOnc Source

World Hematology 2019

World Hematology 2019 welcomes the oncologists, haematologists, immunologists, pathologists, research scholars, industrial professionals and student delegates from biomedical and healthcare sectors to be a part of it.

It has many interactive scientific sessions on different types of Blood disorders and Cancers as well as various diagnostic and therapeutic advancements in this field. It is an initiative to unite the diverse research and business communities working in this field under one roof to explore every single aspect of Oncology and Hematology. 

The conference is focussed on the following topics and sessions:

• Advancements in Hematopoietic cell transplantation
• Anticipating the development of Paediatric Hematology/ Oncology
• Recent trends in diagnosing and treating Hematology/ Oncology indications
• Emerging trends in Cancer Care
• Therapeutic advancements and many more….

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High-dose irradiation before HSCT and risk for malignant neoplasms

Study results shows that, survivors of allogeneic hematopoietic cell transplantation who underwent high-dose total body irradiation incurred nearly 8 times the risk for subsequent malignant neoplasms compared to general population.

Results showed the association to be strongly dose- and fractionation-dependent, and total body irradiation doses for nonmyeloablative conditioning posed no increased risk above that of myeloablative chemotherapy-only based regimens.

“The big takeaway is that people need to be aware of this risk,” Scott Baker, MD, director of the Fred Hutch survivorship program at Fred Hutchinson Cancer Research Center, said in a press release. “For those patients who received high-dose radiation, they need to be especially vigilant about following all the standard cancer prevention and screening recommendations. And younger patients, especially women, should talk to their doctor about starting screening for some cancers, such as breast, at an earlier age than recommended for this general population.”

In the retrospective study, Baker and colleagues evaluated 4,905 patients (57.4% men; 91.8% white) who underwent HSCT between 1969 and 2014 and had survived at least 1 year without subsequent malignant neoplasms. Patients had undergone the transplants for hematologic malignancies (n = 4,500) or nonmalignant conditions (n = 405). Median age at time of transplantation was 34.5 years (range 0.3-78.9),

Risk factors assessed by the researchers included sex, race, age at first transplant, diagnosis for transplant, stem cell source, regimen (including dose and fractionation) and development of graft-versus-host disease as a time-dependent covariate.

Eleven percent of the HSCT recipients (n = 499) developed a total of 581 subsequent malignant neoplasms at a median 10.3 years (range, 1-39.7) after HSCT.

With a median follow-up of 12.5 years (range, 1-42.11) among 1,709 surviving patients,  observed a 22% cumulative incidence of subsequent malignant neoplasms at 30 years post-HSCT.

Compared with SEER population rates matched for age, sex and calendar year, results showed a 2.8-fold (95% CI 2.6-3.1) increase in the standardized incidence ratio of subsequent malignant neoplasms.

The highest SIRs were for subsequent malignant neoplasms in the bones (28.8), oral cavity (13.8), skin (7.3), central nervous system (6) and endocrine organs (4.9).  (EARs) for subsequent malignant neoplasms per 1,000 person-years were seen in cancers of the breast (EAR = 2.2; 95% CI, 1.4-3), oral cavity (EAR = 1.5; 95% CI, 1.2-2) and skin (EAR = 1.5; 95% CI, 1.5-2).

Survivors exposed to either unfractionated (600 cGy-1,200 cGy-1,200 cGy) or high-dose fractionated (1,440 cGy-1750 cGy) total body irradiation had the highest incidence of subsequent malignant neoplasms. Those who received low-dose total body irradiation (200 cGy-450 cGy) demonstrated risk comparable to that of chemotherapy alone, albeit still twice that of the general population.

Patients aged 20 years and younger at the time of transplant had the highest risk for subsequent malignant neoplasms compared with age-matched members of the general population, although this risk decreased with longer follow-up in relation to transplant.

Patients aged 50 and older at the time of transplant showed sustained elevated SIRs over time, although follow-up beyond 20 years for these patients could not be accessed. Those aged 20 years or younger at the time of transplantation had a 2.28-times (95% CI, 1.31-3.96; P = 0.003) higher risk for subsequent malignant neoplasms than patients aged 50 years and older.

Risk for subsequent malignant neoplasms also appeared significantly higher among recipients of cord blood (HR = 3.02, 95% CI, 1.29-7.09) and peripheral blood stem cells (HR = 1.55; 95% CI, 1.16-2.07) vs. bone marrow, including after adjustment for acute and chronic GVHD.

“The ultimate goal for the transplant world is to find effective, nonradiation conditioning regimens, especially for children,” Baker said in the press release.

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Source: https://www.healio.com/hematology-oncology/bone-marrow-transplantation/news/online/%7B87098c14-0bcd-4c14-b775-c99998be6f5c%7D/high-dose-irradiation-before-hsct-increases-risk-for-subsequent-malignancies

Ibrutinib plus R-CHOP improves survival among younger patients with aggressive lymphoma subtype

The addition of ibrutinib to standard R-CHOP chemotherapy improved EFS, PFS and OS among patients aged younger than 60 years with untreated nongerminal center B-cell diffuse large B-cell lymphoma, according to results of a randomized, phase 3 study.

The combination, however, appeared associated with increased toxicity and resulted in worse outcomes among patients aged older than 60 years.

“The interaction between age and toxicity was surprising [because] it was not observed within the context of the phase 1 trial that we have published,” Anas Younes, MD, chief of the lymphoma service and Steven Greenberg chair at Memorial Sloan Kettering Cancer Center. “At the present time, there is no obvious biological explanation, but this will be addressed through planned extensive correlative studies. R-CHOP plus ibrutinib is not commonly given to patients with other types of lymphoma.”

DLBCL accounts for as many as 40% of all lymphoma cases, making it the most common form of lymphoma in the world. A previous phase 1 study appeared to demonstrate the safety of ibrutinib (Imbruvica; Pharmacyclics, Janssen) in combination with R-CHOP chemotherapy — which consists of rituximab (Rituxan; Genentech, Biogen) plus cyclophosphamide, doxorubicin, vincristine and prednisone — among patients with untreated B-cell lymphoma, including DLBCL.

Younes and colleagues specifically investigated whether ibrutinib improves the efficacy of R-CHOP in patients with untreated nongerminal center B-cell or activated B-cell diffuse large B-cell lymphoma.

Researchers randomly assigned 838 patients (median age, 62 years; range, 19-88; 53.3% men) to R-CHOP with ibrutinib at 560 mg daily (n = 419) or with placebo (n = 419) in a 21-day cycle for six or eight cycles, depending upon institutional guidelines.

Three-quarters of the patients (75.9%) had the activated B-cell DLBCL subtype.

EFS among the intent-to-treat population and patients with the activated B-cell subtype served as the study’s primary endpoint. Secondary endpoints included PFS, OS and safety.

Median follow-up was 34.8 months.

Results showed that the addition of ibrutinib to R-CHOP did not improve EFS compared with placebo and R-CHOP in the intent-to-treat population (HR = 0.93; 95% CI, 0.72-1.2) or the activated B-cell population (HR = 0.94; 95% CI, 0.7-1.27).

Ibrutinib also did not increase PFS (HR = 0.91; 95% CI, 0.71-1.18), OS (HR = 0.99; 95% CI, 0.71-1.38) or rates of overall response (89.3% vs. 93.1%) and complete response (67.3% vs. 68%) among the intent-to-treat population.

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Source: https://www.healio.com/hematology-oncology/lymphoma/news/online/%7Bf698cfd3-4f65-4bdb-91c0-50c860dcd560%7D/ibrutinib-plus-r-chop-improves-survival-among-younger-patients-with-aggressive-lymphoma-subtype

CAR T-cell therapy bb2121 shows promising efficacy, manageable toxicity in multiple myeloma

A chimeric antigen receptor T-cell therapy targeting B-cell maturation antigen produced high response rates with manageable toxicity among patients with heavily pretreated relapsed or refractory multiple myeloma, according to results of a phase 1 study. “The adverse events noted in our study were very manageable, and we saw low rates of cytokine release syndrome and neurotoxicity,” Noopur Raje, MD,director of the Center for Multiple Myeloma at Massachusetts General Hospital and professor of medicine at Harvard Medical School.

“[The toxicity] was manageable to the extent that we are now thinking [forward to] outpatient settings. Response rates were high, but we did not see a plateauing of responses in very late-stage multiple myeloma.”

The CAR T-cell therapy bb2121 (Celgene, Bluebird Bio) has shown promise in preclinical studies for treatment of multiple melanoma, for which new therapies have prolonged survival but failed to prevent relapse.

Raje and colleagues reported results from the first 33 patients (median age, 60 years, range, 37-75; men, n = 21) with relapsed or refractory multiple myeloma who received bb2121 in the dose-escalation (n = 21) and dose-expansion (n = 12) phases of the open-label, multicenter trial. All patients had received at least three previous lines of therapy that included a proteasome inhibitor and an immunomodulatory agent or were double refractory. All patients in the dose-escalation cohort and two patients in the dose-expansion cohort had tumor B-cell maturation antigen (BCMA) expression of 50% or greater.

After undergoing lymphodepletion with fludarabine and cyclophosphamide, patients received bb2121 as a single infusion at doses of 50 x 10⁶, 150 x 10⁶, 450 x 10⁶ or 800 x 10⁶ CAR-positive T cells in the dose-escalation phase and 150 x 10⁶ to 450 x 10⁶ CAR-positive T cells in the expansion phase.

Safety served as the primary endpoint. Data cutoff occurred 6.2 months after the last infusion.

Results showed an objective response rate of 85% (95% CI, 68.1-94.9), with 15 patients (45%) achieving a complete response, six of whom have since relapsed.

Median PFS was 11.8 months (95% CI, 6.2-17.8).

Sixteen patients with partial or complete responses appeared negative for minimal residual disease ( 10^-4 nucleated cells).

All 33 patients experienced adverse events, including 28 (85%) who experienced a grade 4 event.

The most common grade 4 hematologic adverse events included neutropenia (n = 26), leukopenia (n = 13), thrombocytopenia (n = 10) and lymphopenia (n = 9). Grade 3 hematologic adverse events included anemia (n = 15), leukopenia (n = 6) and thrombocytopenia (n = 5).

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Source: https://www.healio.com/hematology-oncology/myeloma/news/online/%7Bda1d1336-ff71-467d-a93d-3af4e6294cd5%7D/car-t-cell-therapy-bb2121-shows-promising-efficacy-manageable-toxicity-in-multiple-myeloma

FDA grants orphan drug status to AUTO3 for ALL

The FDA has granted orphan drug status to AUTO3, a cell-based immunotherapy for the treatment of acute lymphoblastic leukemia (ALL).

AUTO 3 (Autolus Therapeutics) is a programmed T-cell therapy containing two independent chimeric antigen receptors targeting CD19 and CD22 that are independently optimized for single-target activity.

“By simultaneously targeting two B cell antigens, AUTO3 is designed to minimize relapse due to single antigen loss in patients with B cell malignancies,” according to a press release from the manufacturer.

“We believe that AUTO3 has the potential to be a best-in-class therapy in pediatric ALL by addressing antigen escape, a common cause of relapse in these patients,” Christian Itin, PhD, CEO of Autolus, said in a press release. “AUTO3 may also provide an improved safety profile over currently marketed CAR T therapies with low levels of severe (cytokine release syndrome) and neurotoxicity observed in clinical studies.”

AUTO3 is currently being tested in pediatric patients with ALL as part of the AMELIA clinical trial and in patients with diffuse large B cell lymphoma in the ALEXANDER clinical trial.

Data from the American Cancer Society suggest there will be 5,930 new cases of ALL and approximately 1,500 deaths in 2019. Sixty percent of cases will be in patients aged younger than 20 years.

The FDA Office of Orphan Products Development grants orphan drug designation to novel drugs and biologics that are intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. The designation allows manufacturers to qualify for various incentives, including tax credits for qualified clinical trials and — upon regulatory approval — 7 years of market exclusivity.

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Source: https://www.healio.com/hematology-oncology/leukemia/news/online/%7Ba0cbd1ae-c5f8-4907-b397-d467ab36ad31%7D/fda-gives-orphan-drug-status-to-auto3-for-all

Calcium and Cancer Risk

Latest research has reported that excess intake of calcium from supplements has been linked to an increased risk for cancer-related deaths.

The report found no mortality benefits associated with any reported dietary supplement use among nearly 31,000 adults in the National Health and Nutrition Examination Survey.

They found that excess calcium consumption was associated with increased risk for cancer-related deaths. Calcium supplements were specifically implicated in the excess of mortality, according to the investigators, with a rate ratio of 1.53 (95% confidence interval, 1.04-2.25) for intakes of 1,000 mg/day versus no intake.

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Source:https://www.mdedge.com/internalmedicine/article/199202/preventive-care/calcium-supplement-use-linked-cancer

Do you know?

Do you know that one pint of blood is capable of saving 3 lives and people suffering from sickle cell disease need up to 4 pints or units of blood every single month to survive.

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Do you Know?

Are you curious to know, why red blood cells are shaped like breath-mint disks with a dent in the middle?

The answer to this query seems interesting, this is because, the breath-mint design allows the cells to twist through capillaries and the tiniest blood vessels. A sphere or cube is less flexible and might get stuck. Also, the dents in the cells add to the surface area, allowing more oxygen and carbon dioxide to pass in and out of the cell.

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World Hematology 2019

Here we have our media partners who support us in making our event. Do join us at Rome, Italy to unravel the conundra in hematology/ oncology. For more details, PS: http://medicines.doctor/haematology5

Alcohol consumption and Multiple Myeloma

Research has shown that high alcohol consumption impairs the immune system and, in turn, increases cancer risk.  However, low alcohol consumption improves insulin sensitivity, which, in turn, decreases risk of diabetes and other obesity-related disorders and thus, indirectly, may decrease risk of multiple myeloma.

Source: https://www.mdedge.com/hematology-oncology/quiz/7735/multiple-myeloma/alcohol-consumption-and-multiple-myeloma?channel=250

Track 18 : Diagnostic and Equipment Market

The major driving factors for hematology and oncology diagnostics market include increasing incidences of blood related disorders and cancers.

The global interventional oncology market is projected to reach USD 2.9 billion by 2024 from USD 2.0 billion in 2019, at a CAGR of 6.8% from 2019 to 2024. The growth of this market is primarily driven by the rising preference for minimally invasive procedures, expansion of the target patient population, increasing public-private funding and government support for cancer research, technological advancements in the field of interventional oncology, and increasing government investments and funding for interventional oncology and related cancer research.

The global hematology diagnostics market size was estimated at USD 5.96 billion in 2017. It is anticipated to expand at a CAGR of 5.85% over the forecast period. Nearly 1 million new cases of blood cancer are expected to be diagnosed by 2020, which is anticipated to account for nearly 6.0% of all new cancer. Furthermore, a significant number of the world population have different hemoglobinopathies. High prevalence of blood disorders, such as thalassemia is anticipated to boost the demand for hematology testing.

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Source of info: https://www.grandviewresearch.com/industry-analysis/hematology-diagnostics-market | https://www.marketresearch.com/MarketsandMarkets-v3719/Interventional-Oncology-Product-Radiofrequency-microwave-12290878/