Let's Talk About Clinical Trials and Lines of Therapy

There are two main types of clinical trials, observational and interventional studies. Observational studies seek to learn information about diseases and populations of patients and do NOT involve making changes in a patient’s treatment. Interventional studies on the other hand seek to learn information about the specific intervention that is being studied and will involve making specific changes in a patient’s treatment with the goal of studying and bettering treatment outcomes.

Often the criteria for patients to qualify for clinical trials can be confusing. Most clinical trials will have very specific criteria for the types of patients that are eligible to enroll. Some may be looking for newly diagnosed patients who haven’t yet started treatment, while others are looking for relapsed or refractory patients who have been on certain types of treatments. In addition to a patient’s treatment history, clinical trials will have a set of criteria that patients must meet, called the inclusion criteria. These include parameters such as lab values that assess the patient’s myeloma, including the monoclonal protein, free light chain, or the presence of a plasmacytoma or lytic lesion that was not previously present. Other common inclusion criteria for clinical trials include lab values that assess the patient’s overall well-being. For example, it is common for an inclusive criteria to require a patient’s platelets count to be higher than 75 Thous/mcl and for the patient to have adequate kidney and liver function.

Clinical trials also have exclusion criteria which prevent patients from qualifying from a particular trial. Common exclusion criteria include the diagnosis of another type of cancer in addition to myeloma and any disorder that might increase a patient’s risk from participating in the trial. Different clinical trials can have different inclusion and exclusion criteria. If you are interested to see if you would fit the criteria for a specific trial you have three non-mutually exclusive options: 1) you may visit the clinicaltrials.gov website to search for all currently active trials. Currently there are 197 active, industry sponsored clinical trials in multiple myeloma, and finding the trial best suited for your particular situation can be daunting; 2) you can contact Sparkcures, that can help you find clinical trials, and 3) you can enroll in All4Cure, where our expert team tracks your status and lets you and your oncologist know about clinical trials or other treatments that we think you and your doctor may wish to consider.

Many clinical trials and drug labels require a patient to have been on previous “lines” of therapy.

But what does a “line” of therapy mean? For example, a recently approved CAR-T cell product, Abecma, is approved for relapsed or refractory myeloma patients who have received 4 or more prior lines of therapy. A “line” of therapy refers to when a patient is given a planned sequence of drugs for at least 1 complete cycle[1]. For example, a patient who is newly diagnosed may create a plan with their oncologist to start induction treatment with Revlimid, Velcade and Decadron followed by an Autologous Stem Cell Transplant and then maintenance therapy with Revlimid. This would all count as 1 line of therapy because this is a planned sequence.

What circumstances would arise that would result in a new line of therapy?

A new line of therapy occurs when a patient has an unplanned addition or substitution of 1 or more drugs in an existing regimen[1]. For example, if a patient started induction therapy with Revlimid, Velcade, and Decadron but added Darzalex during cycle 4, the addition of Darzalex would constitute a new line of therapy. Another situation that would result in a new line of therapy would be changing an entire regimen due to progression. In the example above, if a patient was on maintenance Revlimid but then progressed and stopped Revlimid and required new treatment with Kyprolis, Pomalyst and Decadron, the addition of those drugs would qualify as a new line of therapy.

References:

1. S. Vincent Rajkumar, Paul Richardson, Jesus F. San Miguel; Guidelines for determination of the number of prior lines of therapy in multiple myeloma. Blood 2015; 126 (7): 921–922. doi: https://doi.org/10.1182/blood-2015-05-647636