Ibrutinib (Imbruvica) Enhances Survival for Younger Individuals with Diffuse Large B-cell Lymphoma

 

Addition of ibrutinib (Imbruvica) to a standard chemotherapy regimen can enhance survival for some younger individuals with a specific form of diffuse large B-cell lymphoma (DLBCL), as per the reanalysis of data.

The findings, published in the Journal Cancer Cell, come from a new analysis by researchers at the USA’s National Cancer Institute (NCI) of a previously conducted phase-3 clinical trial.

 

Diffuse large B-cell lymphoma is the most common type of lymphoma, accounting for 40 percent of lymphoma cases at the global level. The individuals with the diffuse large B-cell lymphoma are typically treated with R-CHOP, which includes vincristine, cyclophosphamide, doxorubicin, prednisone, and the monoclonal antibody rituximab. But R-CHOP therapy is not useful for everyone with diffuse large B-cell lymphoma.

 

Ibrutinib (Imbruvica) was the first targeted therapy to be assessed for the treatment of diffuse large B-cell lymphoma. It inhibits the function of Bruton tyrosine kinase, a protein that is involved in the growth and survival of B cells. Cancerous cells of the ‘active B cell-like’ (ABC) subtype of diffuse large B-cell lymphoma require this protein in order to survive.

 

A trial named PHOENIX was launched in the year of 2013 to assess the effectiveness of adding ibrutinib to R-CHOP therapy for newly diagnosed patients which do not have the ‘germinal centre B cell–like’ (GCB) type of diffuse large B-cell lymphoma.

 

Outcomes published in 2019 demonstrated that overall, combination of ibrutinib and standard chemotherapy regimen did not help patients with non-germinal centre B cell–like diffuse large B-cell lymphoma in order to live longer.

 

Although, patients aged under 60 years did have improved event-free survival and overall survival, but as this was a secondary endpoint of the trial its significance has remained controversial.

 

Therefore, in this latest study, researchers of the National Cancer Institute as well as their collaborators evaluated the tumour biopsy samples from patients on the trial.

 

They have now concluded that patients aged under 60 years with MCD and N1, specific genetic subtypes of non-germinal centre B cell–like diffuse large B-cell lymphoma, had an exceptional response to the combined therapy or treatment.

All of those patients are alive without disease 3 years following diagnosis.

According to Study co-author Dr Wyndham H. Wilson, senior investigator in the Lymphoid Malignancies Branch, “This new analysis offers a compelling rationale for health specialists to consider addition of ibrutinib (Imbruvica) along with the standard chemotherapy for the initial therapy of younger individuals with non-germinal centre B cell–like diffuse large B-cell lymphoma.”

 

Following the completion of genetic analyses on tumour samples from 773 of the 838 participants and determining their subtypes, researchers found that most of the benefit from ibrutinib (Imbruvica) was in patients with ABC diffuse large B-cell lymphoma.

 

Out of the 4 genetic subtypes of ABC diffuse large B-cell lymphoma, it was found that those patients aged 60 and under with the MCD subtype had 3-year event free and OS rates of 100 percent with ibrutinib (Imbruvica) and R-CHOP. This is compared to 3-year event free survival of 48 percent and 3-year OS of 69.6 percent with R-CHOP alone.

 

Younger individuals with the N1 subtype also had 3-year event-free and OS (overall survival) rates of 100 percent with ibrutinib (Imbruvica) and R-CHOP, in comparison to 3-year event-free and OS of 50 percent with R-CHOP alone.

Individuals with the genetic subtype named BN2 did not benefit from the addition of the ibrutinib (Imbruvica), but this subtype already has an 82 percent OS rate with R-CHOP alone.

Ibrutinib (Imbruvica) was also effective for some other younger individuals with the non-germinal centre B cell–like diffuse large B-cell lymphoma, although the researchers were not able to specify benefits for the A53 subtype.

According to Dr Louis M. Staudt, chief of the Lymphoid Malignancies Branch in the Center for Cancer Research at NCI, “For years we have only had chemotherapy and rituximab to offer these individuals (patients). Now, we expect that the addition of ibrutinib (Imbruvica) to current therapy may provide younger patients a better chance of surviving this aggressive cancer.”

Dosage and Administration of Artesunate

 

Indications & Usage: Artesunate for Injection (Injectable artesunate) is introduced as a first line treatment and recommended by WHO for the initial treatment of severe malaria in adult as well as pediatric patients.

In order to treat severe malaria with injectable artesunate should always be followed by a full or complete treatment course of an apt oral antimalarial regimen.

Limitations of Use: The artesunate an anti-malaria medication does not treat the hypnozoite liver stage forms of Plasmodium and will therefore not prevent the relapses of malaria because of the Plasmodium vivax or Plasmodium ovale. Concomitant therapy with an antimalarial agent such as an 8-aminoquinoline drug is required for treating the severe malaria due to P. vivax or P. ovale.

 

Dosage Forms and Strengths: The injectable artesunate is available as the strength of 110 mg for Injection. It comes as a sterile white or almost white, fine crystalline powder in a clear glass single-dose vial for constitution.

 

Dosage and Administration: The recommended dosage and administration of Artesunate for Injection in adult and pediatric patients is 2.4 mg/kg administered, should be intravenously at 0 hours, 12 hours, and 24 hours, and thereafter, administered once daily until the patient is able to tolerate the oral antimalarial therapy. Administer constituted artesunate injection intravenously as a slow bolus over one minute to two minutes. Do not administer artesunate injection via continuous intravenous infusion. The artesunate injection should be administered with an antimalarial agent that is active against the hypnozoite liver stage forms of Plasmodium, such as an 8-aminoquinoline drug, to patients with the severe malaria due to P. vivax or P. ovale.

 

Preparation of Artesunate for Injection for Intravenous Administration: The Artesunate Injection needs to be constituted with the supplied diluent before administration. A diluent consisting of 12 mL of sterile 0.3 M pH 8.0 sodium phosphate buffer is provided with Artesunate for Injection.

To constitute artesunate injection, withdraw 11mL of this diluent through a needle and syringe and inject into the artesunate vial (when constituted the final concentration of artesunate is 10 mg/mL). Swirl gently (avoid shaking) for up to five to six minutes until the powder is completely dissolved and no visible particles remain.

The parenteral drug products need to be inspected visually for particulate matter and discoloration before administration, whenever solution and container permit. It is not advised to administer the Artesunate for Injection in case particulate matter and/or discoloration is observed.

Following constitution, inject the constituted solution intravenously (through an established intravenous line or needle) as a slow bolus over one to two minutes. It is advised to discard the vial and also any unused portion of the medicine product following use.

 

Storage of the Constituted Solution: The constituted solution of Artesunate Injection should be administered within 1.5 hours of constitution with the supplied diluent.

Tocilizumab Side Effects and Precautions

 

Tocilizumab is a prescription medicine named an interleukin-6 (IL-6) receptor antagonist. The

medical uses of tocilizumab are listed as follows:

●       Tocilizumab is used to treat adults with moderately to severely active rheumatoid arthritis (RA) after at least one other medicine called a disease modifying antirheumatic drug (DMARD) has been used and did not work well.

●       Tocilizumab is used to treat adult patients with giant cell arteritis (GCA).

●       Tocilizumab is used to treat patients with active polyarticular juvenile idiopathic arthritis (PJIA) aged 2 years and older.

●       Tocilizumab is used to treat patients with active systemic juvenile idiopathic arthritis (SJIA) aged 2 years and older.

●       Tocilizumab is used for slowing the rate of decline in lung function in adults with systemic sclerosis-associated interstitial lung disease (SSc-ILD) (also named scleroderma-associated ILD).

It is not specified if the drug Tocilizumab is safe and effective in children with PJIA or SJIA aged under two years or in children with conditions other than PJIA or SJIA.

 

Possible Side Effects: The most important side effects of Tocilizumab Injection are:

Serious infections: Tocilizumab is a medication that affects your or your child’s defense system. Tocilizumab can fade the ability of your or your child’s defense system in order to fight infections other than COVID-19. This drug can make you or your child more likely to get infections or worsen any infection that you or your child have, other than COVID-19.

 

Tears (perforation) of the intestines or stomach: Some individuals with Tocilizumab get tears in their intestine or stomach. This occurs most often in those individuals who also administer the NSAIDs (nonsteroidal anti-inflammatory drugs), methotrexate, or corticosteroids.

 

Liver problems (hepatotoxicity): Certain individuals taking treatment with Tocilizumab have experienced severe life-threatening liver problems, which needed a liver transplant or led to death.

 

Changes in certain laboratory test results: Your or your child’s health specialist should  do blood tests before you or your child start receiving Tocilizumab. You or your child should not receive this medicine in case your or your child’s white blood cells or platelet (blood cells that help with blood clotting and halt bleeding) counts are reduced or your or your child’s liver function tests are extremely high.

 

Allergic reactions: Inform your or your child’s health specialist right away in case you or your child have signs and symptoms such as rash, swelling of your lips, tongue, or hives (raised red patches of skin which are often very itchy), or throat. This may indicate that you or your child are having an allergic reaction.

 

Nervous system problems: While rare, Multiple Sclerosis has been diagnosed in those who take Tocilizumab. It is not specified what effect Tocilizumab may have on some nervous system disorders.

 

The most commonly noted side effects of Tocilizumab injection include:

●       headache

●       increased blood pressure (hypertension)

●       injection site reactions

●       upper respiratory tract infections (common cold, sinus infections)

 

Tocilizumab & Pregnancy: Inform your health specialist in case you are planning to become pregnant, are pregnant, plan to breast-feed, or are breast-feeding. You and your health specialist should decide if you will take therapy with Tocilizumab or breast-feed. You should not do both.

Warnings and Precautions of Sorafenib

 

Sorafenib is introduced to treat liver cancer (hepatocellular carcinoma), kidney cancer (advanced renal cell carcinoma), and thyroid cancer (differentiated thyroid carcinoma). The sorafenib a multikinase inhibitor may also be known as a so-called multikinase inhibitor. It acts by slowing down the rate of growth of cancer cells and cutting off the blood supply that keeps cancerous cells growing.

Sorafenib comes in the form of tablets you can take at home. Take sorafenib twice daily. Take the sorafenib tablets with a glass of water at a persistent time each day. The sorafenib tablets should be taken without food or with a low-fat meal. In case you are going to have a high-fat meal, take sorafenib tablets at least one hour prior to or two hours after your meal.

 

WARNINGS AND PRECAUTIONS:

Pregnancy and Lactation: Females should not become pregnant while on sorafenib therapy. Females of childbearing age must be apprised of the potential hazard to the fetus, which includes teratogenicity, and embryotoxicity. Sorafenib therapy should not be used during pregnancy. Also, breastfeeding should be discontinued during Sorafenib therapy.

 

Dermatological Toxicities: Hand-foot skin reaction (palmar-plantar erythrodysaesthesia) and rash represent the most common adverse medicine reactions with Sorafenib. The rash and hand-foot skin reactions (Grade 1 & 2) generally appear during the initial six weeks of therapy with Sorafenib. As noted in one clinical study, the incidence of hand-foot skin reaction may be greater in the Asian group. The management of dermatologic toxicities may include topical therapies for symptomatic relief, temporary treatment interruption or dose modification of Sorafenib, or in severe or persistent cases, permanent discontinuation of Sorafenib.

 

Hypertension: An increased incidence of hypertension was observed in patients treated with Sorafenib. Hypertension was noted mild to moderate at the beginning of the therapy and was amenable in order to manage with the standard antihypertensive therapy. Blood pressure should be monitored regularly and treated, in case needed, in accordance with standard medical practice. In cases of severe or persistent hypertension, or hypertensive crisis despite apt antihypertensive therapy, permanent interruption of sorafenib therapy should be considered.

 

Aneurysms and artery dissections: The VEGF pathway inhibitors used in patients either with or without hypertension can promote the development of aneurysms or artery dissections. Prior to starting Sorafenib therapy, this risk should be precisely considered in all those patients who are with hypertension or a history of aneurysm.

 

Haemorrhage: An increase in the risk of bleeding may occur following the use of Sorafenib. The incidence of serious bleeding events is uncommon. If any bleeding event necessitates medical intervention, it is recommended that permanent discontinuation of therapy with Sorafenib should be considered. Because of the risk of bleeding, bronchial, tracheal, and oesophageal infiltration needs to be treated with localised therapy before administration of Sorafenib in patients with DTC-Differentiated Thyroid Carcinoma.

 

Warfarin: The infrequent bleeding events or elevations in the International Normalised Ratio (INR) have been observed in certain patients taking warfarin while on Sorafenib therapy. Patients concomitantly with warfarin should be monitored regularly for changes in prothrombin time, INR, and for clinical bleeding episodes.

 

Wound Healing Complications: No formal studies of the effect of concomitantly on wound healing have been conducted. In all those patients who are undergoing any major surgical procedures, temporary interruption of Sorafenib tablets therapy is required just for precautionary reasons. There is limited clinical experience regarding the timing of reinitiation of therapy after major surgical intervention. Thus, the intent to resume Sorafenib therapy after any major surgical intervention should be based on behalf of the clinical judgment of adequate wound healing.

 

Gastrointestinal Perforation: Gastrointestinal perforation has appeared as an uncommon event and has been reported in less than one percent of patients taking treatment with Sorafenib. In certain cases, this was not linked with an apparent intra-abdominal tumour. The sorafenib therapy should be discontinued if gastrointestinal perforation develops.

 

Hepatic Impairment: Experience in Child-Pugh B hepatic impairment is limited. No data is available on patients with Child-Pugh C (severe) hepatic impairment. Since sorafenib medication is mainly eliminated through the hepatic route, exposure could be increased in patients with severe hepatic impairment.

 

Drug-induced Hepatitis: Drug-induced hepatitis has been noted in post-marketing experience. Sorafenib should be interrupted if drug-induced hepatitis is suspected.

Hypocalcaemia: When using Sorafenib in patients with differentiated thyroid carcinoma, precise monitoring of blood calcium level is required. As per clinical trials, hypocalcaemia was observed more frequently and more severely in patients with DTC, especially with a known history of hypoparathyroidism, in comparison to patients with renal cell or hepatocellular carcinoma.

TSH Suppression in Differentiated Thyroid Carcinoma (DTC): In the Differentiated Thyroid Carcinoma clinical trials, increases in TSH levels above 0.5mU/L were noted in patients treated with Sorafenib. When using Sorafenib in differentiated thyroid carcinoma patients, precise monitoring of TSH levels is needed.

Combination of Enasidenib & Azacitidine Significantly Improves Overall Response Rate in AML

 

A new study published in The Lancet Oncology suggests that the combination of enasidenib (Idhifa) and azacitidine are well tolerated and offer improved overall response rate (ORR) in recipients with newly-diagnosed IDH2-mutant acute myeloid leukemia (AML) compared with azacitidine monotherapy.

Enasidenib is specifically a small molecule, oral inhibitor of isocitrate dehydrogenase 2 (IDH2) inhibitor. The current standard of care in acute myeloid leukemia is induction together with myeloablative intensive chemotherapy.

For all those recipients who are not chemo eligible, either due to age or due to poor performance status, lower-intensity strategies are used. These include low doses of chemo and the consideration of targeted agents with FLT3 or IDH2 mutations.

The phase 1/2 findings compared azacitidine monotherapy to the experimental addition of azacitidine and enasidenib. The primary end points are dose-limiting toxicities, AEs, ORR, and pharmacokinetics. Secondary end points basically include event-free survival, complete remission, hematologic improvement rate, OS, duration of response, one-year survival, and time to response.

Phase-1 b assessed the efficacy, along with tolerability, and also clinical activity of the addition. During phase-2, the addition was compared head to head with azacitidine monotherapy.

In terms of safety, 91 percent of patients in the addition group and 81 percent of patients in the monotherapy group experienced adverse events. The common adverse events included thrombocytopenia, vomiting, neutropenia, anemia, and nausea.

Oxaliplatin: Antineoplastic medicine

Oxaliplatin is the medicine sold under the trade name Eloxatin. Oxaliplatin is an antineoplastic drug, which helps treat patients with stage III colon cancer and advanced colorectal cancer. It helps in the treatment of patients suffering from stage III colon cancer and advanced colorectal cancer. It comes in the form of lyophilized powder for solution in injection.

The active ingredient is Oxaliplatin and Lactose monohydrate is the inactive ingredient present in the medicine. The standard strengths of the medicine are 50 mg and 100 mg. According to the professionals, the general dosage of Oxaliplatin 100 mg is to give in combination with the other drug 5-fluorouracil/leucovorin every two weeks. This medicine has numerous side effects: allergic reaction, fatigue, abdominal pain, skin disorder, reaction at the injection site, nausea, diarrhea, vomiting, stomach-related problems, fever, infection, etc. 

One should only administer Oxaliplatin 100 mg injection according to the prescription of the healthcare professionals. Not every patient experiences these side effects of the medicine; if in case of side effects or an overdose of medication, consult the doctor for worsening of signs and symptoms. 

In India, there are numerous certified suppliers of such rare medicines that offer medicines at a lower price than innovators'. Ikris Pharma Network is one such trusted and certified supplier, and Oxaliplatin price is readily available at a reasonable price here. Ikris supplies medicines and medical aids in India and overseas.  

All about comparator drug

Comparator drugs are also known as reference-listed drugs. These drugs have already been approved and have a license. Also, these drugs are already being used in the market to treat patients. Comparing new generic versions with reference-listed drugs shows the biochemical similarity, having the same active ingredient and effect on patients. In its regulatory submissions, a drug company seeks approval to market a generic equivalent and refers to the Reference Listed Drug. 

There is heavy demand for alternatives to generic medicines in the pharmaceutical industry. Heavy demand for alternative generic medicines results in pressure on pharmaceutical companies to frame robust strategies for selecting a Comparator drug and then sourcing and maintaining an uninterrupted supply of that drug to all trial sites in a cost-effective manner. 

The top 10 pharmaceutical companies together spend more than $20 million every year on comparator sourcing. Innovators or drug producers, wholesalers, and local distributors can carry out direct comparator sourcing. 

Participation of Ikris in pharma industry as comparator drug sourcing

Ikris Pharma Network is an internationally acclaimed pharmaceutical wholesaler and service company. It has specialization in sourcing Comparator drug(s)/ innovator samples from worldwide (countries like India, USA, Europe, Canada, Australia, New Zealand, Korea, Japan, and Latin America). Ikris specifically is a one-stop source for all your requirements of innovator samples (single batch/multiple batches of specific quantities) for clinical trials as well as bioequivalence studies.

We have an internationally established supplying network that helps us procure, store, and provide the products from all the major pharmaceutical manufacturers and authorized distribution channels to and from any locations in the world, specific product sets in a bit huge volumes. We only work with approved sources and validated supply chains.

We have expertise in cold chain shipping and international customs requirements, which helps us ensure that the temperature-sensitive study drugs arrive within the required temperature range at the clinical trial facilities. We use reliable transportation that caters to cold, ambient, and everyday storage and delivery requirements. 

We provide regular updates and advise of product shortages or manufacturer delays allowing you to stay one step ahead and plan your study accordingly. 

We work with the best logistics and courier partners, which enable us to efficiently get your Comparator drug supply to you on or ahead of time.

Our Comparator drug sourcing service included:

• Clinical Trial Services 
• Investigational Medical Products and Comparators
• Rescue medication
• Co-medication
• Analytical samples