Lung Cancer Timeline: Growth, Spread, and Prognosis

In Chronic Myeloid Leukemia, Are Patients Setting The Right Course For Themselves?

Effective therapies have led to improved survival for individuals with chronic myeloid leukemia (CML). However, treatment is generally lifelong, and nonadherence is common, which decreases the likelihood of achieving an optimal response to therapy. Patients who intentionally stop their therapy say they have a higher symptom severity than patients whose reasons for nonadherence are unintentional, such as in cases where they can't afford their medication.

The Bottom Line

A new study enrolled 94 patients with CML and asked them to self-report, via online questionnaires, their adherence to therapy.

The vast majority of patients (92.5%) reported optimal adherence, defined as taking at least 90% of their prescribed CML medication during the 6-month study period.

Both patients and physicians found the data-gathering platform easy to use and a valuable asset in the treatment and management of CML.

As some patients can attest to, clinicians often underestimate the impact of adverse events during routine care. With this in mind, a team of researchers recently conducted a pilot trial across the U.S. And Italy of an online system for monitoring patient-reported symptoms in newly diagnosed CML. The investigators hypothesized that this approach could increase clinicians' awareness of patients' symptom burden, positively impacting treatment adherence and potentially improving clinical outcomes.1

Capturing patients' self-reports

Two centers in the U.S. Enrolled 16 patients with newly diagnosed CML, and 13 centers in Italy enrolled 78 patients, for a total of 94 participants.1 Their median age was 57 years (range, 19 to 82 years), 55% were men, and 42% of the total cohort had low Sokal risk scores. Patients were instructed to report their symptoms on a wireless tablet provided at the time of a clinical visit and just before the physician consultation. During the consult, a graphic display of the patient's symptoms was available to the physician in real time.

The primary outcome measure was pill count adherence, which the investigators averaged for each patient over the 6-month follow-up period to assess the overall rate of adherence. Patients' self-reported treatment adherence was also captured. The secondary objectives included assessing the feasibility and acceptability of the approach to both patients and physicians, as well as the proportion of optimal responders to tyrosine kinase inhibitor (TKI) therapy at 3 and 6 months using European LeukemiaNet criteria.

The prespecified feasibility threshold for the monitoring system was 80% of participants completing the online questionnaires on >60% of follow-up visits. However, only 68.5% (63 of 92 evaluable patients) satisfied this requirement, so the feasibility threshold was not met.

How well did patients do?

Optimal adherence, defined by the investigators as taking at least 90% of prescribed TKI therapy during the trial, was achieved by 86 patients (92.5%). Patient questionnaires, separate from the pill count, also revealed a high level of self-reported adherence. Optimal response to TKI therapy was achieved by 69 of 79 (87.3%) and 61 of 81 (75.3%) patients at 3 and 6 months, respectively.

Patients found the online system easy to use, and at 3 months, 73 of 78 (93.6%) agreed or strongly agreed that it helped them to communicate better with their treating physician. At 6 months, the percentage slipped a touch, to 86.6% (71 of 82 of patients). At 3 months and 6 months, all 21 physicians who used the platform agreed that it was easy to use and that the information it gathered had helped them manage their patients more effectively.

The trial met its primary outcome measure of treatment adherence, due to the 92.5% of evaluable patients who took at least 90% of their prescribed TKI therapy. The authors speculated that the fact that the intervention was implemented very early in the disease course, at the point of treatment initiation, optimized the system's effectiveness.

Assessing the study's main take-aways

The large proportion of optimal responders in this study (87.3% at 3 months and 75.3% at 6 months) was similar to that observed in pivotal randomized controlled trials, which found that patients who achieve early molecular response have significantly better long-term outcomes than nonoptimal responders do. Early molecular response also predicts stable deep molecular response, a prerequisite to treatment-free remission.

Although the web-based platform was well accepted by patients and physicians alike, the timing of the study may have negatively impacted its feasibility, as patient enrollment took place during the pandemic, between July 2020 and August 2021, when hospitals were often overwhelmed. The findings of this study will therefore need to be further confirmed by a large-scale randomized controlled trial that uses standard monitoring.

The study authors concluded that patient-reported symptom monitoring, starting at the initiation of CML therapy, "may be critical to improve adherence to therapy and early molecular response rates."1 Future research, they added, will hopefully be able to "assess the value of this approach in improving long-term clinical and survival outcomes."1

Published: January 25, 2024

Cheryl Zigrand is a freelance medical writer who writes across multiple disease states, including oncology, dermatology, and rheumatology. She is based in Brooklyn, N.Y.

Drugs For Treatment Of Chronic Myeloid Leukemia

Are you searching for medications to treat 'Chronic Myeloid Leukemia'? Welcome to this section, which serves as a repository for medications that are relevant to the treatment of Chronic Myeloid Leukemia. The page includes both the generic and brand names and can be an invaluable resource for healthcare professionals and individuals who wish to get an insight on different medication options. Click on a medication below to view details including brand names, prices, dosages, side effects, and administration guidelines. Additionally, a FAQs section is available for each medication, addressing popular inquiries and providing deeper insights into its use for Chronic Myeloid Leukemia management. We recommend consulting your doctor to verify the information presented on this page or for any additional clarifications. Advertisement Brand Names and Generic Names of Drugs for Treatment of Chronic Myeloid Leukemia Anagrelide Anagrelide is a platelet-reducing agent prescribed for thrombocythemia. Bosutinib Bosutinib is a kinase inhibitor, prescribed for chronic myelogenous leukemia (CML). Advertisement Busulphan Busulphan is a chemotherapy agent, prescribed for chronic myelogenous leukemia. Chlorambucil Chlorambucil is a cytotoxic chemotherapy drug, prescribed for chronic lymphocytic leukemia, non-Hodgkin's lymphoma, Hodgkin's disease and lymphosarcoma. Trade Names : Cytarabine Cytarabine is a chemotherapy agent, prescribed for acute myeloid leukemia (AML) and non-Hodgkin lymphoma. Trade Names : More... Advertisement Dasatinib Dasatinib is prescribed for blood cancer(Chronic Myeloid Leukemia). Trade Names : Daunorubicin Daunorubicin is a chemotherapeutic agent, prescribed for acute myeloid leukemia and acute lymphocytic leukemia. Trade Names : Doxorubicin Doxorubicin is a cytotoxic anthracycline antibiotic, prescribed for treating various types of cancer. Trade Names : More... Fosfestrol Fosfestrol is a hormonal chemotherapy agent, prescribed for malignant neoplasms. Trade Names : Hydroxyurea Hydroxyurea is an antineoplastic agent, prescribed for sickle cell anemia, several types of cancer (such as melanoma, chronic myelogenous leukemia, squamous cell carcinomas), as an adjunct to antiretroviral therapy for AIDS. Trade Names : More... Leucovorin Leucovorin is a folic acid analog, prescribed for reducing the toxic effects of methotrexate. Trade Names : More... Methotrexate Methotrexate is an antimetabolite, curative in choriocarcinoma (cancer of the tissue that normally would develop into placenta). Trade Names : More... Mitoxantrone Mitoxantrone is an antineoplastic agent, prescribed for metastatic breast cancer, acute myeloid leukemia, non-Hodgkin's lymphoma, and acute lymphoblastic leukaemia. Trade Names : Omacetaxine Mepesuccinate Omacetaxine Mepesuccinate is an antineoplastic agent (protein translation inhibitor), prescribed for chronic myeloid leukemia (CML). Prednisone Prednisone regulates the symptoms of low corticosteroid levels, and is used to treat arthritis, severe allergic reactions, multiple sclerosis, lupus, and certain conditions that affect the lungs, skin, eyes, kidneys blood, thyroid, stomach, and intestines. Trade Names : More... Rituximab Rituximab is a monoclol antibody, prescribed for certain types of cancer such as lymphomas, leukemia, transplant rejection and some autoimmune disorders. Trade Names : Vincristine Vincristine is a chemotherapy agent, prescribed for certain types of cancer such as leukemia, Hodgkin disease, and non-Hodgkin lymphomas. Trade Names : Search for Drugs: For Related Medical Condition Suggested Readings on Chronic Myeloid Leukemia Acute lymphoblastic leukemia (ALL) is the cancer of white blood cells characterized by excess lymphoblasts. It is the most common of all childhood cancers and can be fatal in weeks if left untreated. Acute myeloid Leukemia, more popularly known by its abbreviated form AML, is a fast- evolving leukemia that affects both children and adults alike Chronic Lymphocytic Leukemia (CLL) is one of the most common types of adult leukemia and is considered as one of the 'good cancers'. Encyclopedia section of medindia gives general information about Leukemia Non Hodgkins Lymphoma is a cancer that affects the lymph tissues. It is made up of a wide array of subtypes. Hodgkins lymphoma or Hodgkins disease has the distinction of being the first cancer to be cured by chemotherapy or by radiotherapy. 'Chemo' means medicine or 'drug'; 'therapy' means 'treatment'. Chemotherapy refers to the use of cytotoxic drugs in cancer treatment. Chemotherapy drugs perform like 'magic bullets' to destroy cancer cells in the body. Hairy cell leukemia (HCL) is a type of leukemia where there are increased numbers of abnormal B-lymphocytes, a type of white blood cells. Childhood or pediatric cancers occur in children less than 15 years of age. They are rare and differ from adult tumors in their location and behaviour.

Chronic Myelogenous Leukemia (CML) Has An Answer Now!

Another plant extract called Forskolin has been found to be helpful in inhibiting the growth of chronic myelogenous leukemia (CML) cells in cultures and mice by up to 90 percent. Forskolin is prepared from the root of the plant coleus forskohlii, a native of India that is used as an alternative remedy in other countries, and as an ornamental plant in the US.

CML, a malignant cancer of the bone marrow, results from mistakenly exchanging genetic material in chromosomes 9 and 22 during cell division. The translocation creates a new, fused gene (called BCR-ABL), that produces an enzyme called Bcr-Abl, which permanently "turns on" cell growth signals that are normally controlled by another group of enzymes phosphatases. Because of Bcr-Abl, production of white blood cells gets out of control, leading to CML.

At the early stage (chronic phase), the disease almost always responds to the anticancer drug Gleevec, which puts Bcr-Abl on hold. The drug was hailed as the first "wonder drug" for cancer when the Food and Drug Administration (FDA) approved it for CML treatment five year ago.

However, the disease has proven difficult for some patients. In a minority of patients who initially responded well to Gleevec, they acquired new mutations and developed resistance to the drug. In these patients, proliferation of white blood cells continues, leading the disease to the final (acute stage) called the blast crisis, where immature white blood cells infiltrate the blood and bone marrow.

Clinicians know the signs and symptoms of the different stages of CML, but until now, they are clueless about what causes the disease to progress.

In collaboration with an international group of researchers, Dr. Danilo Perrotti at the Ohio State University not only found the plant extract that effectively inhibits cell growth of CML, but also found that the progression of CML is due to the increased activity of Bcr-Abl enzyme.

Advertisement

Bcr-Abl stimulates a protein called SET, which, in turn, suppresses the phosphatase PP2A. PP2A acts otherwise as a tumour suppressor in the blast crisis, applying the brakes to growth signals stuck in the "on" position. When PP2A isn't working properly, cancer cells grow uncontrolled.

Earlier studies by Perrotti showed forskolin could restore PP2A function. In the current study, Perrotti and his research team tested the effects of forskolin on normal, Gleevec-sensitive and Gleevec-resistant CML cells, and discovered that the extract restored normal PP2A function, reduced the cancer cells' growth by up to 90 percent, and induced the death and differentiation of leukemia cells.

Advertisement

Forskolin had no adverse effects on the normal cells. It is currently used in Japan as a broncho- and vaso-dilator. It has been tested and found safe in clinical trials in Austria, among patients with asthma. The FDA has not approved it for use in the US.

In the study, Perrotti and his team treated leukemic mice with forskolin and then discontinued the treatment for a couple of weeks. After resuming the treatment, they observed that forskolin blocked Bcr-Abl activity and reinstated normal cell functioning in the mice that received forskolin, while others without treatment died.

The findings are significant because they may yield new treatment options – especially those with advanced CML, or who become resistant to the drug Gleevec.

"We believe these are significant findings," said Perrotti. "We have uncovered a key process that underlies progression in CML and identified an agent that can block it. We also have shown that forskolin can reinstate normal cell functioning, even in Gleevec-resistant cells that do not respond to any treatment currently available."

CML affects one or two people per 100,000 and accounts for 7 to 20 percent of cases of leukemia. Ionizing radiation is believed to trigger the chromosome abnormality that leads to CML. It takes years to develop CML.

---