Subcutaneous Rituxan for FL

Interesting research in The Journal of Clinical Oncology on how Rituxan is delivered to Follicular Lymphoma patients with low tumor burden. I think it has the potential to change how patients get Rituxan. As someone who was in this exact situation, I find it particularly interesting.

The article is called "Randomized Phase III Trial Evaluating Subcutaneous Rituximab for the First-Line Treatment of Low–Tumor Burden Follicular Lymphoma: Results of a LYSA Study," and as the title says, it reports on the results of a phase III clinical trial.

A little background first. Some FL patients are able to have just Rituxan as a first treatment. Typically, this happens with patients with a fairly slow-growing type of FL with low tumor burden. 

What exactly is "low tumor burden"? It took me much longer to find an answer than it probably should have, but this write up for a clinical trial from 2004 defines it this way:

• Must meet the following criteria for low tumor burden:

  • No nodal or extranodal mass at least 7 cm
  • Less than 3 nodal masses greater than 3 cm in diameter
  • No systemic symptoms or B symptoms
  • No splenomegaly greater than 16 cm by a computed tomography (CT) scan
  • No evidence of risk of compression of a vital organ (i.e., ureteral or epidural)
  • No leukemic phase with greater than 5,000/mm^3 circulating lymphocytes

  • No cytopenias, defined as any of the following:

    • Platelet count less than 100,000/mm^3
    • Hemoglobin less than 10 g/dL
    • Absolute neutrophil count less than 1,500/mm^3

 To put it simply, the affected lymph nodes need to be a certain small size, there can't be too many of them, blood counts have to be close to normal, and the nodes can't be affecting any vital organs. When I was diagnosed, I was low tumor burden. Two years later, some nodes had grown big enough that they were blocking something and making my leg swell up. Time for Rituxan!

So for the phase III trial described in this article, a group of 202 FL patients were divided randomly into two groups. The first group received intravenous Rituxan, once a week for four weeks, intravenously, with a line into the arm or hand.  This is usually the way patients receive Rituxan, and it was the way I received it (except I had it for 6 weeks instead of 4).

The second group had one round of intravenous Rituxan, but then had four more weekly rounds of subcutaneous Rituxan (a shot from a needle, rather than a line going into the arm). Subcutaneous Rituxan usually goes in faster, so it saves time and money for everyone. In addition to these four rounds, this second group also had subcutaneous Rituxan Maintenance -- four more rounds, every two months. That's a little different than Rituxan Maintenance usually works. It's usually every two months for two full years.

So the study wanted to find out more about two things -- first, is the Subcutaneous Rituxan more effective than the Intravenous Rituxan? And second, is this shorter Maintenance schedule better than the usual longer one?

It's kind of a funny study, because it's not really comparing two of the same things. The Maintenance adds some extra treatment that makes it hard to compare IV and SC Rituxan. It's not comparing apples to apples. It's more like apples to apple pie with ice cream.

And the researchers know that and acknowledge it.

The study's main way of measuring was Progression Free Survival -- how long it took for the disease to come back.  The 4-year PFS was 58.1% for the Subcutaneous group, and 41,2% for the IV group. 

The Complete Response Rate was higher for the Subcutaneous group (59%) than the IV group (36.6%). But there were no differences in the Time to Next Treatment or Overall Survival.  

In conclusion, the researchers found that it wasn't the Subcutaneous delivery that resulted in better outcomes, but in getting more Rituxan early on.

And that makes sense.  More treatment = more results.

What's important here, in the end, is that is shows that Rituxan Maintenance can be helpful without stretching it out for two years. One of the problems with such long Maintenance is that the treatment lowers immunity, since it wipes out B cells. Doing that for 4 weeks is OK, but doing it for 2 years could result in some immunity problems and make the patient more vulnerable to infections. A shorter time might be a batter balance of good results with good safety.

However, the researchers also point to some limitations. It is possible, for example, that a higher dose of Rituxan right away will be more effective (since Subcutaneous Rituxan allows for a higher dose). It's also possible that the "maintenance" isn't necessary, and just stretching out the dosing to three months might be more effective than 4 weeks (the good results came in the first three months, not in month 5, 7, or 9).

So, in the end, the study probably raises more questions than it answers. And that's OK. A someone who benefited from Rituxan only as a treatment, I'd love to be able to see more people have it, and avoid more aggressive treatments if they can. And if a study like this helps us rethink something so successful, then I'm all for it.

More research to come soon. Thanks for reading.