Novartis to partner with Penn in development of chimeric antibody T-cell program

Exciting news yesterday:
Novartis and Penn enter into multi-year collaboration to study chimeric antigen receptor (CAR) technology for the treatment of cancer!

Here is one of the news stories from NJ newspaper.And another from a pharma news site.

See my prior post on my own visit to Penn to see if I may benefit from this therapy.

What is exciting here, as Dr Sharman points out in his new CLL and Lymphoma Blog, is that this partnership may increase access to this potentially curative therapy, not only in terms of clinical trials, as the 10 patients or so who have undergone this therapy were in a privately funded pilot study, but also to mainstream if the technique continues to be useful and is licensed by the FDA.

We can only hope this approach pans out. Some potential drawbacks are noted by Sharman and also in a post on CLLTopics, highly recommended because this therapy is not without its downside...

Started Arzerra!

To update my situation up to yesterday:

• Bone marrow: packed with small lymphocytes, no sign of Richter's
• PET scan many lymph nodes, no sign of activity suggestive of Richter's
• quite enlarged spleen, easily palpable by even myself, as well as increasing axillary nodes
• whew!
• ongoing need for platelet transfusion once weekly, at least made it 2 weeks between RBC

So from the 2 or 3 options  for treatment my onco team picked Arzerra (ofatumumab) in part because I have already had rituximab 3 times and Campath not so good for nodal disease and has significant immune suppression...

Got the first dose, in slowly increasing amounts by infusion, to total 300 mg, in hospital yesterday. Because of a high rate of infusion reactions, my oncos wanted to do as inpatient. It went well, no reaction, since they load you with steroids, antihistamines and acetaminophen. The problem was the inherent inefficiency in hospital, I arrived at direct admission office at 9, got to the floor, IV in place at 10 AM but did not get premeds until about 1:30 and Arzerra started about 2:30, and finally done at 10PM. Felt good though and elected to go home by my usual train/bus combo, enjoying the exuberance of youth, first the disgruntled Phils fans on the train (another story there, they are having a sucky year), and about 40 teenagers coming from a concert in Camden jammed on the bus. I knew where to stand so got the first seat up front, so could get off easily, home by 12:30, slept like a baby.

Next week dose of Arzerra is 2000mg and I will bend over backward to arrange as outpatient, which since I had no reaction, should be able to convince my oncologists.

Although I had blood work on admission, I forgot to ask for results -- I had profuse bleeding from IV site on removal last night requiring a pressure dressing but no problems today. Since have been requiring platelets once weekly, I will go on Monday and get another count.

Rearranging deck chairs on the Titanic

I finished the workup of my leukemic relapse, having had a bone marrow biopsy and PET/CT over the last week and a half and in 2 days visit my oncologist to learn the results and find out what the next treatment regimen is. I had to have another RBC and platelet transfusion last week, less than a week after the last. These have become more frequent making me wonder if my anemia and thrombocytopenia are due to more than bone marrow failure, perhaps hypersplenia, which my oncologist has mentioned as a possibility in the past. Adding to this possibility is that I can now feel a very firm mass in my left upper quadrant that is probably spleen (confirmed by internist last week on routine followup visit, see below). I would think our first step would be to treat the leukemia and see how my counts respond to get a better idea about whether drug-induced marrow failure and/or hypersplenism are contributing to my significant and worsening transfusion dependence. My last count was Hgb 7.6, WBC 57K, and platelets a dangerously low 8K, see photo of my arm from a routine blood test, demonstrating how much we all need platelets.

So I also saw my internist this past week as routine follow-up, primarily on mild hypercholesterolemia and a previous slightly raised PSA. I was very worried about the latter since it could mean I had early prostate cancer, something I certainly did not want to deal with given my leukemia relapse. Thankfully the value this time was normal. My LDL (bad) cholesterol was low and I also had low testosterone (which is funny since one of my company's clients is the maker of a testosterone replacement product). I complained of my quite painful nighttime leg cramps and the doc said to either try CoQ10 (a borderline alternative product found in vitamin aisle that is not cheap) and/or stop my statin since my cholesterol never that high and have no significant or personal family history of heart problems. I asked about testosterone replacement but had to admit any symptoms of lack of energy, sexual interest, etc were more likely due to the leukemia. My doc actually had me laughing (?gallows humor) when he said these problems he was managing were like rearranging the deck chairs on the Titanic. I think that this is no doubt true and now can just focus on getting better with the next treatment, God willing.  

Here is what my internist meant, the leukemia is my main problem and I could be going down, but I am here to tell you, NOT WITHOUT A FIGHT!

T-Cell Chimeric Antigen Receptor pilot trial at Penn

Saw Dr Porter at Penn today, for a second opinion for the first time, thinking I may be interested in the chimeric antigen receptor in vitrio genetically modifying T-lymphocyte pilot trial (I know that is a mouthful, see here for explanation). I have been needing both platelet and RBC transfusions almost every 2 weeks since I finished my 6 cycles of bendamustine-rituximab at the end of March. My last WBC count showed a rising lymphocyte count and I have noticed that some of my lymph nodes have started to increase in size a bit. Dr Porter felt, as does my regular oncologist at Hahnemann/Drexel, that I need to have my bone marrow checked again as well as repeat CT scans, to better determine if my low counts are due only to the leukemia coming back or perhaps in part also bone marrow failure as a treatment-related adverse event, maybe even myelodysplasia.... He suggested that the next treatment could be ofatumumab (a monolclonal antibody supposedly more effective than rituximab) or either rituximab or alemtuzumab (Campath) with high dose methylprednisolone, stating that Campath is not so effective by itself. The response to this therapy would help to determine whether my marrow is showing just leukema or some underlying dysplasia. Stem cell transplant may be an option if it looks like my marrow is not performing well, but it would have to be from an unrelated donor (see prior post - unless I can get my brother to help me out), but If my marrow seems to be OK than an option would be this T cell tiral or perhaps one of the small molecule tryosine kinase inhbitors under development. Time will tell, but not having a good response to B-R after 3 prior treatments with fludarabine shows my disease is advancing.....

Finished 6 cycles of Treanda/Rituxan...only PR

My last treatment with Treanda (bendamustine) and Rituxan (rituximab) was late March, at that time, prior to the infusion, my CBC showed total WBC 22K. Hb 7.8 and platelets 22K. A month later the CBC = 8K total WBC, 8.7 Hb (after weekly Procrit and one transfusion) and 36K platelets, the only normal value being the white cell count. Since then the total WBC peaked at 30 and then down to 16K last week but both Hgb and platelets sliding slowly downward to 6.4 and 16K respectively, leading to another RBC and platelet transfusion last week... Bottom line: My markedly enlarged lymph nodes have decreased significantly in size but my marrow is not yet cleared AND/OR still recovering from bendamustine suppression.... 

 So my oncologist has suggested I look into consultation with Dr Porter at U Penn who a few months ago published a study in which genetically engineered T cells led to good results in 3 patients with CLL (see article or for any layfolk reading this), so I have an appointment in early July (maybe sooner if my medical record and request for stat consult for a fellow MD are heeded) 

 My doc has talked also about using another monoclonal antibody Campath (alemtuzumab) which is good for ongoing bone marrow disease but hard on one's immune system, particularly T cells. One has to get weekly checks of CMV reactivation with the aim to treat if this bad virus comes back with a very expensive drug, worth it if one wants to avoid retinitis!

 New drugs in the pipeline that have gotten a lot of press are oral tyrosine kinase inhibitors, now in phase III trials (see this) but these trials may not work for me, because I have had Rituxan 3 times already:

• for GS-1101, the active arm is Gs-1101 and Rituxan vs placebo and Rituxan
• for  ibrutunib (PCI32765) it would be the drug vs  ofatumumab (a CD 20 Monoclonal not necessarily any better than Rituxan

there is an earlier phase trial for a drug similar to ibrutinib (AVL-292) that has a small phase I trial that I could go to NYC for but would need to have a platelet count over 30K

I tried to get into Revlimid phase II trials but in the spring of 2011 my disease was not advanced sufficiently and in the fall I failed to qualify because my platelet count was under their criteria. Phase III trials are drug vs placebo + BR which I have just completed with only partial remission so not for me..

So I am running out of options, and need to think about stem cell transplant also. My brother who matches me well has stopped communicating with me and may not be  interested in saving my life, but I will keep trying....

Halfway through 6 cycles of Treanda/Rituxan

So my lymph nodes everywhere are at least half the size they were before treatment, my WBC total is down to 17K from over 70K, and my platelets have rebounded from treatment-related low of 20K to close to where I started. On the downside I had the one hospitalization for fever with borderline neutropenia, 1 platelet transfusion, and 4 PRBC transfusions. Still have anemia, last Hb 7.1 but getting weekly Epogen. Hope to tolerate the drugs better in the next 3 cycles, with the help of pretreatment Decadron and post-treatment Neulasta. Even more I hope for normalization of my lymphocyte count and continued shrinkage of nodes. Will I get a prolonged remission? Should i consider a second opinion at U Penn, should I look into a maintenance trial if available? Time will tell....

O'Brien on oral tyrosine kinase inhibitors

Dr. Susan O'Brien on kinase inhibitors, interview with Andrew Schoor --

Bottom line:
CAL-101 (now known as GS-1101) and PCI-32765 have shown great results with little myelosuppression. Moving quickly to later phase trials as monotherapy or in combo with chemo and or immunotherapy. Dr O is excited, the FDA is excited as am I if and when my next relapse occurs.....