Pomalidomide (Pomalyst) Update For Relapse After 15 Doses – March 19 2013

Tuesday, 19 Mar 2013: I’ve taken 15 doses of Pomalidomide (Pomalyst) in Cycle 1 for my relapsed myeloma. I should have had my blood tested today, but Dr. Padavanija is out-of-town and they scheduled me for Friday, 22 Mar 2013 at St. Luke’s Hospital in Twin Falls, Idaho.

I’ve decided that I’m way too puffy and effected from Dex 40 mg weekly on Tuesday’s, so I lowered the dose to 30 mg today, dividing it in 2 doses (breakfast 15 mg and dinner 15 mg). I’ll discuss this with the doctor on Friday at my appointment.

Again, the St. Luke’s Hospital MSTI Boise Pharmacist called today to check on my Pomalyst side effects. Not much different than last week except I am constipated.

  • burning scalp (improving a lot)
  • creepy legs (had before I started Pomalyst, but seems worse at night – haven’t taken much oxy this week (maybe two doses of 1/4 tab).
  • increased neuropathy of left leg especially from knee to groin – was about a 2 (1-10 scale) prior to Pomalyst and now 4. I am attributing my left hip pain to neuropathy now since all of my tests (plain x-rays and MRI were normal). At times, I had right hip pain too.
  • tired, especially after taking – serious fatigue each afternoon – can’t do anything. Easily out of breath, but lungs are clear with no cough. Don’t let these walk photos fool you in to thinking I’m leading a normal life – I AM NOT!
  • constipation – working with 2-3 Senna-S nightly and 2 Phillips Magnesium tablets nightly – without much success. Experience GI reflux on dex day (Tuesday).
Monday, 18 Mar 2013:  No gastritis at all this day. Walked the Mine Hill with Jani and the dogs this afternoon. 0.71 miles at a 4 percent grade up and then down to Jonah at the Cattle Guard. Jonah had a flat tire over the weekend they found a nail in the tire this morning.
Kemmer and me. ICY COLD WIND

Jani, Zoe, Kady, and Kemmer with Mt. McCaleb in the background – Jani ended up walking the Kemmer and Zoe (sisters from the same litter who will be 5 years old on 6 Apr 2013) all the way home and I drove from the Cattle Guard with 12 year-old Kady.

Monday night into Tuesday, I had terrible neuropathy and creepy legs and was unable to sleep…most probably from the Mine Hill walk Monday.

Tuesday, 19 March 2013: I was too tired to do much today. Jani went with Ron rock hunting.
She found a geode.

And a lucky horseshoe for me!



Pomalidomide (Pomalyst) Update For Relapse After 7 Doses – March 12 2013

Absolutely NO sleep last night – My gastrointestinal track has just STOPPED all of a sudden and I suffered all night. Took Senna-S and Phillips Tab – hope things start up again SOON.

Took half of my weekly 40 mg Dex for the day with breakfast (20 mg). Will take the second half with dinner since I take my Pomalyst at bedtime.

My GI tract started back up, but, I am still distended in my abdomen.

Update after first 7 days of pomalidomide (Pomalyst) 4 mg. Drove to Lost Rivers Medical Center in Arco, Idaho (30 miles each way) and had my blood drawn to see how my bone marrow is reacting to the new Pomalyst. They had not received my blood draw order from St. Luke’s Hospital in Twin Falls, Idaho and I had to call them to get the order which came quickly, but lacked the LDH which should have been drawn – oh well.

My labs are not much different than before I started the Pomalyst 4 mg. My white blood cell count (WBC)  is low at 2.2 (norms 4.5-11 and reflects your ability to fight infection); ANC (absolute neurtrophil count  is low at 1.36 (norms 1.9-8.8 and reflects your immune system quality and whether you can be in public with or without a mask); hemoglobin low at 9.2 (norms 12-16 and reflects your oxygen carrying capacity or energy level) and platelets low at 97 (norms 140-440 and reflects your ability to clot your blood). I hope my platelets hang in there throughout the Cycle 1 (21/28 days).

My kidney function tests via my blood continue slightly abnormal. My creatinine is slightly high at 1.10 (norms 0.52-1.04); BUN is normal at 14.4 (norms 7-17); and GFR is abnormally low at 53 (norms > 60). My liver function tests are back to normal since I stopped plain Tylenol.
Drove back to Mackay and pretty much slept all day on the sofa…had to make up for that sleepless night.  Had a little gastritis, but nothing too bad.

The St. Luke’s Hospital MSTI (Mountain States Tumor Institute) Pharmacist from Boise called today to ask me about any side effects that I’ve had from the Pomalyst. They have to report side effects to the manufacturer, Celgene, and they will be calling me each week. I explained that the only side effects that I could attribute to Pomalyst were:
  • burning scalp (improving)
  • creepy legs (had before I started Pomalyst, but seems worse at night – taking 1/4th to ½ tabs of plain Oxy which helps. Trying to balance dosage so I don’t feel hung over during the day)
  • increased neuropathy of left leg especially from knee to groin – was about a 2 (1-10 scale) prior to Pomalyst and now 4. I am attributing my left hip pain to neuropathy now since all of my tests (plain x-rays and MRI were normal).
  • tired, especially after taking
  • constipation (I forgot to tell her this, I will next week)
My neighbors this morning.


Pomalidomide (Pomalyst) Update For Relapse After 5 Doses – March 10 2013

Update on side effects of pomalidomide (Pomalyst) after five (5) 4 mg doses. I take the pomalidomide just before bedtime because it makes me almost instantly tired.

  • continued scalp burning
  • creepy legs with a fullness feeling in left calf (like it is being blown up with bicycle pump)
  • neuropathy of left leg rated 4 on 1-10 scale, especially from back of left knee to left hip
  • neuropathy of left foot is mild
  • poor sleep attributed to neuropathy
  • tiredness, especially in afternoons and evenings
  • no diarrhea and no constipation
I have been experimenting with small doses of oxy (1/4 tabs) to relieve the neuropathy and not leave me feeling hung over while awake. The scalp burning might freak me out, but since I know this was only a temporary sign after I started Revlimid (a relative of pomalidomide), I’m fine with it.

My gastritis is GREATLY improved – I’m sure it is caused by dex and not pomalidomide. I take 40 mg of dex by mouth each Tuesday. Almost instantly develop gastritis BURNING PAIN after taking dex and by Friday had very little to no gastritis this week.

Continue nightly Fragmin 15,000 unit injections to thin my blood and prevent blood clots from pomalidomide.

Have been walking Kemmer daily – 0.82 miles on 7 Mar 2013; 1.28 mile on 8 Mar 2013; and 1.28 miles on 9 Mar 2013. My back hurts across my scapula when I walk, but that was happening even before I was officially diagnosed with myeloma.  It is still winter here in Idaho and COLD. My hair is still growing and I think I even need a haircut to even it out.

Able to do laundry, house cleaning, etc. without problems. In addition, I feel like I am clear of thinking of late.

Pomalidomide (Pomalyst) Update For Relapse – After 2 Doses – March 7 2013

Day 1, 5 Mar 2013 I started on 4 mg of pomalidomide (Pomalyst) the evening of 5 Mar 2013. Just like Revlimid, I thought it best of take in the evening since Revlimid made me tired and pomalidomide is in the same family with Revlimid. 

I also took 40 mg of oral Dex (each tablet is 4 mg, so I have to take 10 for 40 mg). The oral Dex almost instantly cured my creepy leg syndrome, but it wasn’t long before I had good case of gastritis going AGAIN. I took Carafate Suspension and that helped some, but the best cure for my gastritis is a slice of lightly toasted bread. I attribute the gastritis to the dex and not the pomalidomide. 

So far, I think the only side effect that I’ve had after one capsule of pomalidomide is being tired almost immediately after taking it. I slept well from 7 PM until 11 PM. After that I didn’t sleep too well, but I stayed in bed and only watched television for about 2 hours around 1 AM.

Day 2, 6 Mar 2013 I had continued gastritis. Around 4 PM, my creepy legs returned with a vengeance which I’m pretty sure is from the pomalidomide and I had a frontal headache which I thought might be from our cloudy, off-and-on snowing weather today. I ate dinner early and the headache disappeared. Had another poor night of off and on sleep. I finally took 1/4 tab of oxy (a little medicine goes a long way with me) around 2 AM for my creepy legs and slept until 6:45 AM – this is good.

Day 3, 7 Mar 2013, gastritis. Up this morning, clear of thinking and don’t feel hung-over from the 1/4 tab of oxy last night. Mild gastritis. No creepy legs this morning. I do have a burning sensation over the crown of my head, but it does not itch. I had a similar, but WORSE burning and itching when I started Revlimid, but it dissipated after about a week and never returned.

Summary of “maybe” Pomalidomide Side Effects:

  • tired after taking
  • very creepy legs
  • burning scalp sensation

Approved for Pomalidomide (Pomalyst) For Relapse – March 4 2013

My medical insurance company approved pomalidomide (Pomalyst) with no copay for me today. FedEx will deliver the medication tomorrow and I’ll get started on it 5 March 2013 for my recent relapse on top of my old relapse – haven’t had less than 40% plasma cells in my bone marrow since 50 days after my 2nd autologous stem cell transplant which was done on 18 May 2012. Currently my bone marrow biopsy plasma cell count is at 60%. 

Let’s hope pomalidomide (Pomalyst) works for me and I can tolerate it. I was unable to take Thalidomide when I was first diagnosed due to severe neurological side effects (unable to think or ambulate). I did fine on nearest relative, Revlimid. Initially, during induction prior to my 1st autologous stem cell transplant on 9 July 2011, I had a Revlimid itchy rash on my scalp and belly, but that quickly dissipated. Revlimid also causes diarrhea. Crossing my fingers for pomalidomide…. 

The MRI of my left hip and pelvis done on 28 Feb 2013 was negative, so I have no idea why it hurts.

Have enjoyed my almost 3 week chemo-free holiday since 14 Feb 2013. My gastritis is much improved. However, it is unnerving knowing my bone marrow is probably producing plasma cells as I type. I have taken dex during this time, but no chemo. And I continue on my Fragmin 15,000 units nightly injections.

Energy is up and I’ve been walking Kemmer almost daily. I was able to do my volunteer work with the Mackay Food Bank and I enjoyed that – even if I had to wear a mask!


Dex, MRI, Pomalidomide Approval Sought For Relapse – February 28 2013

The 40 mg of Dex I had yesterday pretty much kept me awake all night, but I kept busy with watching television and doing computer work.

Went to Walmart (wore my N95 mask) before my MRI of the hip and pelvis appointment at 10:15 AM. I’m so used to wearing this mask, it doesn’t phase me when people stare.

At St. Luke’s Hospital Radiology, I discovered they had me come 1 hour early to fill out 3 pages of paperwork (fortunately, I had a written summary of all my previous tests with me, which helped in filling the form out), get my clothes changed with no metal, and be ready for the MRI Exam. The MRI Exam took 1 1/2 hours and technician Melissa was very good about explaining time frames to me. I was happy to have the ear plugs and ear muffs.  I must have fallen asleep in the MRI Scanner because it didn’t seem like 1 1/2 hours.

Had a call from the St. Luke’s Hospital MSTI (Mountain States Tumor Institute) Pharmacy and they are working hard to get me approved for the pomalidomide. I have to call Celgene and complete a Pomalidomide SURVEY – basically to assure I cannot get pregnant and will not share the medication with others and not donate blood since this medication is a derivative of thalidomide (known to cause severe birth defects). This SURVEY has to be filled out every 6 months. I called and talked to my Anthem Insurance Transplant Coordinator RN letting her know that they were requesting pomalidomide for me. Now, I just have to wait to hear about the decision. Pomalidomide (Pomalyst) costs $10,500 for a 21 day supply.

Drove home to Mackay on dry roads. Just as I arrived home at 3 PM, it began to snow.

The 40 mg of Dex has my face puffy with bright red cheeks. Don’t look at my weird hair….

Fell asleep on the sofa late afternoon and slept until 9 PM. Got up and went to bed and couldn’t sleep AGAIN…but, I stayed in bed all night without any technology to keep me awake.


Bone Marrow Biopsy Results and MORE – February 27 2013

Drove to Twin Falls, Idaho in very cold Minus 2 temperatures, which gradually warmed up as I left the Big Lost River Valley and approached the Magic Valley.

Highway 93 to Carey, Idaho. Look in the middle and you’ll see an avalanche chute.
I delivered my 24 hour urine collected from 26-27 Feb 2013 kept in a cooler with ice to the St. Luke’s Hospital Lab. 


My appointments at St. Luke’s Hospital, Twin Falls was all mixed up and they didn’t have me down for a lab draw prior to my doctor’s appointment and no Infusion Room appointment. So, I waited while very nice receptionist Pamela got it figured out for me.

My hair is growing again and I actually have bangs!…me and Michelle Obama!  However, my hair is WILD and won’t do anything I try to do with it. I had to shave my legs for the first time this morning for a very little stubble.

They finally drew my blood from my Bard Power Port and and waited while the results were done. Dr. Padavanija came in and told me my 10th bone marrow biopsy results “weren’t good”. 

Evidently, I have been looking at the apples to oranges vs apples to apples on my previous bone marrow biopsy results. When I reported that my plasma cell percentage in my bone marrow was 60 percent on 16 Oct 2012 and then down to 40 percent on 20 Dec 2012, I was reporting TWO DIFFERENT methods – flow cytometry for plasma cells and a manual count of plasma cells from the slides. Evidently, the manual count for plasma cells is the most accurate. You’d think I know this before the 10th Bone Marrow Biopsy!!!

On 16 Oct 2012, the flow cytometry was 27 % plasma cells and the manual count was 60 %.
On 20 Dec 2012, the flow cytometry was 40 % plasma cells and the manual count was not done. Dr. Padavanija sent Pathology a request to do it today, and the manual count was 50 %.
On 20 Feb 2013, the flow cytometry was 26 % plasma cells and the manual count was 64 %.


On the cytogenetics report, I have two lines of abnormalities with a final note indicating, “This result is indicative of persistent disease. The findings of abnormal metaphases in a patient with myeloma is also an indicator for increased cell proliferation, which has been shown to be predicative for shorter event-free and overall survival (Haematologica, 96(1): 87’11). Clinical correlation is required.”

My peripheral blood on 20 Feb 2013 was summarized as:
1. Moderate anemia with slight macrocytosis (oxygen carrying ability and energy)
2. Severe leukopenia/neutropenia (ability to fight infection)
3. Moderate thrombocytopenia (ability clot blood)

SPEP Blood Values from 20 Feb 2013:

My M-Spike was sligthtly down to 0.3 (20 Feb 2013) from 0.4 (22 Jan 2013 and 20 Dec 
2012).
M-Spike Hx since 2nd ASCT (autologous stem cell transplant):
20 Feb 2013      0.3 (Idaho)
22 Jan 2013      0.4 (UCH)
20 Dec 2012     0.4 (Idaho)
27 Nov 2012     0..5 (Idaho)
20 Nov 2012     0.5 (Mayo Scottsdale)
16 Oct 2012      0.3 (UCH)
2 Oct 2012        0.4 (Idaho)
4 Sep 2012       0.3 (Idaho)
13 Aug 2012     0.1 (Idaho)
8 Aug 2012      <0.1 (Idaho)
18 May 2012     2nd ASCT (UCH)

My M-Spike history is not very valuable since I am a non-secretory myeloma patient where the bone marrow values are more valuable than the blood values.

Total Protein: normal at 6.3 (norms 6-8.2)

IgG low at 556 (norms 700-1600)
IgA low at <13 (norms 70-400)
IgM low at <8 (norms 40-230)

Lamba Qnt FLC results BELOW reportable range of 1.9 (norms 5.7-26.3)
Kappa Qnt FLC 3.64 (norms 3.3-19.4)
Kappa/Lamba FLCR Unable to calculate ratio since values below reportable range.

Dr. Padavanija called Clay Smith, MD at the University of Colorado while I waited today, 27 Feb 2013 and they decided my bone marrow biopsy results mean I have failed on carfilzomib/dex/revlimid with a couple of cytoxan doses. I will discontinue carfilzomib/revlimid/ and cytoxan today. 

They will attempt to get approval to put me on pomalidomide (Pomalyst) 21 out of 28 days and Dex 40 mg (Days 1, 8, 15, 22. The approval of the pomalidomide may take weeks, but they wanted me to start the Dex 40 mg today. I asked if I should continue Revlimid 10 mg until the decision is made on the pomalidomide and Dr. Padavanija said no. So, I will continue off chemotherapy for another week or 2. Hopefully, my lab values will have time to recover during this time. 

The good news is that pomalidomide (Pomalyst) is a pill taken daily at home and I will not have to go to St. Luke’s Hospital two days a week with a motel stay like I have been doing for carfilzomib chemotherapy. I will have to week blood tests once I start pomalidomide.

The Myeloma Beacon had an article about a French study on polalidomide today [French Study Provides Further Insights Into Pomalyst’s Efficacy, Safety, And Dosing
[ by Virginia Li | Feb 27, 2013 4:47 pm |] which was interesting. Click here to go to article:
http://www.myelomabeacon.com

Today’s lab values:
White blood cells (WBC) continue low at 2.1 (norms 4.5-11); Absolute neutrophil count (ANC) continues low at 1.25 (norms 1.9-8.8); hemoglobin continues low at 9.8 (norms 12-16); and platelets continue low at 128 (norms 140-440).
My LDH was up at 633 (norms 313-619), a gross indicator of inflammation and rapid cell growth.

My kidney function blood test showed an increase in creatinine again to 1.11 (norms 0.52-1.04).

I received my monthly bone building medicine, Aredia 30 mg intravenously. I took over-the-counter Claritin and 500 mg of Tylenol to decrease the headache, body aches, and flu like symptoms of Aredia. 

I received the  40 mg of dex intravenously today since my stomach has been so upset. Dr. Padavanija said the IV Dex would also upset my stomach. She gave me a prescription for Carafate 1 GM/10 ml Suspension to be taken 4x per day which will be hard for me since it has to be taken on an empty stomach not within eating for 1 hour before or 2 hours after eating and not within 30 minutes of taking any antacids…we’ll see how I do…because I’m a snacker.

They were able to schedule the MRI of my hip and pelvis for tomorrow morning, 28 Feb 2013, so I kept my motel reservation for tonight, 27 Feb 2013 even though I didn’t get any chemotherapy today and I won’t get any tomorrow. 

I also got a new prescription for oxycodone 5 mg immediate release tabs to replace my use of Tylenol and Percocet (which has Tylenol in it). They are very small pills, but I think I can cut them in half for a 2.5 mg dose.

Happily went to Taco Bell for dinner!  :) That part of my life GOOD!


Pomalidomide and Light Chain Amyloidosis

With the immunomodulatory drug pomalidomide (Pomalyst) recently approved for patients with multiple myeloma who have progressing disease within 60 days of the last of at least 2 prior therapies which had to have included lenalidomide (Revlimid) and bortezomib (Velcade), its an opportune time to review what we know (and don’t know) about the drug in light chain (AL) amyloidosis. 

Pomalidomide, like lenalidomide, is a structural analogue of thalidomide. The structures of each are shown here:

source: http://www.readcube.com/articles/10.1186/2162-3619-1-27

The FDA-approved dose of POM in multiple myeloma is 4 mg/day for 21 out of every 28 days.

Investigators at the Mayo Clinic have studied POM (with dexamethasone) in 33 patients with previously treated AL amyloidosis. Patients had had a median of 2 prior therapies, with about half having had autologous stem cell transplant. A few (7) had previously been treated with other immunomodulatory drugs. 

The initial dose of POM in this study was 2 mg/day for 28 consecutive days each cycle (no break). DEX was given at 40 mg/week. POM dosing could be adjusted upward (if no response) and downward (for toxicity). The doses actually received are shown here: 

source: http://bloodjournal.hematologylibrary.org/content/119/23/5397.long

About half of the patients had hematologic responses, with the majority of these being partial. The median duration of response was 19 months. A handful of patients who had hematologic responses also had improvement in organ function, which is about what would be expected (based on prior work involving transplant, bortezomib, and other agents). Some of the responses observed occurred in patients who had had prior lenalidomide. 

A few notes regarding toxicity/adverse events: mild hematologic and gastrointestinal events were common. Peripheral sensory neuropathy (numbness, tingling) was documented in almost all patients – this was generally mild, but was more common than one might expect from, say, lenalidomide (at least in myeloma patients). The authors noted that the cardiac biomarker NT-pro-BNP (a marker of heart failure) sometimes worsened even in the setting of a hematologic response. Similar discordance between light chain measurements and cardiac markers have been noted previously in AL patients treated with immunomodulatory drugs (take a look).  In the present study, a 30% rise in the NT-pro-BNP in the first 3 months of therapy was associated with inferior survival, even though some such patients had concurrent light chain improvement.  

What we know: 
  • POM can (and undoubtedly will) be used as treatment for AL amyloidosis. 
  • Responses can be seen even in patients who have had prior autologous stem cell transplant, bortezomib, or lenalidomide.
What we don’t know: 
  • Optimal dose, schedule, and duration of POM in AL amyloidosis (tsk! details!) 
  • Mechanism of NT-pro-BNP increase with POM therapy.
Study Spotlight: 

POM, like lenalidomide and thalidomide, will be studied in combination with other active drugs in patients with AL amyloidosis. The Karmanos Cancer Institute will be coordinating a national trial investigating the combination of POM, bortezomib, and dexamethasone in AL amyloidosis. This is the first trial prospectively studying an immunomodulatory drug combined with a proteasome inhibitor as front-line therapy for AL amyloidosis.  Participating centers will include Boston University, Duke University, the Colorado Blood Cancer Institute (Denver, CO) and Princess Margaret Hospital (Toronto).  

Pomalidomide Approved By the FDA – February 8 2013 – May be on my horizon if carfilzomib fails to continue to drop my bone marrow plasma cell percentage below 40%.

U.S. FOOD AND DRUG ADMINISTRATION APPROVES POMALYST® (POMALIDOMIDE) FOR THE TREATMENT OF PATIENTS WITH RELAPSED AND REFRACTORY MULTIPLE MYELOMA

Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.

Supporting the approval were the results of MM-002, a phase II, randomized, open-label study evaluating pomalidomide (4 mg once daily on days 1-21 of each 28-day cycle) plus low-dose dexamethasone (40 mg per day given only on Days 1, 8, 15 and 22 of each 28-day cycle for patients 75 years or younger, or 20 mg per day given only on Days 1, 8, 15 and 22 of each 28-day cycle for patients greater than 75 years of age) versus pomalidomide (4 mg once daily on days 1-21 of each 28-day cycle) alone in patients with relapsed multiple myeloma who were refractory to their last myeloma therapy and had received lenalidomide and bortezomib.

Of the 221 patients that were evaluable for response, 29.2% (95% CI 21.0, 38.5) achieved a partial response or better in the pomalidomide plus low-dose dexamethasone arm compared to 7.4% (95% CI 3.3, 14.1) in the pomalidomide-alone arm. Overall Response Rate was based on responses assessed by the Independent Review Adjudication Committee (IRAC) based on the European Group for Blood and Marrow Transplantation (EMBT) criteria. The median duration of response for patients in the pomalidomide plus low-dose dexamethasone arm was 7.4 months (95% CI 5.1, 9.2) while the median has not yet been reached for the pomalidomide alone arm.

POMALYST is an analogue of thalidomide, is contraindicated in pregnancy and is only available through a restricted distribution program called POMALSYT REMS.TM Deep venous thrombosis (DVT) and pulmonary embolism (PE) occur in patients with multiple myeloma treated with POMALYST. Please see full Prescribing Information, including Boxed WARNINGS, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.

In the study, 219 patients were evaluable for safety. The most common grade 3 or 4 adverse reactions (≥15%) in the pomalidomide plus low-dose dexamethasone arm versus pomalidomide alone respectively, were neutropenia (38% and 47%), anemia (21% and 22%), thrombocytopenia (19% and 22%), and pneumonia (23% and 16%). 

POMALYST will only be available in the United States through POMALYST REMS,™ a restricted distribution program.



POMALYST® is a registered trademark of Celgene Corporation

About POMALYST®
POMALYST® oral therapy comprises pomalidomide, an IMiDs® compound. POMALYST and other IMiDs compounds continue to be evaluated in over 100 clinical trials.

POMALYST® (pomalidomide) is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.

Important Safety Information
WARNING: EMBRYO-FETAL TOXICITY and VENOUS THROMBOEMBOLISM
Embryo-Fetal Toxicity
· POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting POMALYST treatment
· Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping POMALYST treatment

POMALYST is only available through a restricted distribution program called POMALYST REMSTM.

Venous Thromboembolism
· Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE) occur in patients with multiple myeloma treated with POMALYST. Prophylactic anti-thrombotic measures were employed in the clinical trial. Consider prophylactic measures after assessing an individual patient’s underlying risk factors

CONTRAINDICATIONS: Pregnancy

·       POMALYST can cause fetal harm and is contraindicated in females who are pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus
·       Pomalidomide is a thalidomide analogue and is teratogenic in both rats and rabbits when administered during the period of organogenesis.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity
·       Females of Reproductive Potential: Must avoid pregnancy while taking POMALYST and for at least 4 weeks after completing therapy. Must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with POMALYST, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of POMALYST therapy. Must obtain 2 negative pregnancy tests prior to initiating therapy. 
·       Males: Pomalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 28 days after discontinuing POMALYST, even if they have undergone a successful vasectomy. Males must not donate sperm
·       Blood Donation: Patients must not donate blood during treatment with POMALYST and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST

POMALYST REMS Program
Because of the embryo-fetal risk, POMALYST is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called “POMALYST REMS.” Prescribers and pharmacists must be certified with the program; patients must sign an agreement form and comply with the requirements. Further information about the POMALYST REMS program is available at [celgeneriskmanagement.com] or by telephone at 1-888-423-5436.

Venous Thromboembolism: Patients receiving POMALYST have developed venous thromboembolic events reported as serious adverse reactions. In the trial, all patients were required to receive prophylaxis or antithrombotic treatment. The rate of DVT or PE was 3%. Consider anticoagulation prophylaxis after an assessment of each patient’s underlying risk factors.

Hematologic Toxicity: Neutropenia of any grade was reported in 50% of patients and was the most frequently reported Grade 3/4 adverse event, followed by anemia and thrombocytopenia. Monitor patients for hematologic toxicities, especially neutropenia, with complete blood counts weekly for the first 8 weeks and monthly thereafter. Treatment is continued or modified for Grade 3 or 4 hematologic toxicities based upon clinical and laboratory findings. Dosing interruptions and/or modifications are recommended to manage neutropenia and thrombocytopenia.

Hypersensitivity Reactions: Patients with a prior history of serious hypersensitivity associated with thalidomide or lenalidomide were excluded from studies and may be at higher risk of hypersensitivity.  
                                 
Dizziness and Confusional State: 18% of patients experienced dizziness and 12% of patients experienced a confusional state; 1% of patients experienced grade 3/4 dizziness, and 3% of patients experienced grade 3/4 confusional state. Instruct patients to avoid situations where dizziness or confusion may be a problem and not to take other medications that may cause dizziness or confusion without adequate medical advice.

Neuropathy: 18% of patients experienced neuropathy (approximately 9% peripheral neuropathy). There were no cases of grade 3 or higher neuropathy adverse reactions reported.

Risk of Second Primary Malignancies: Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.

ADVERSE REACTIONS
In the clinical trial of 219 patients who received POMALYST alone (n=107) or POMALYST + low-dose dexamethasone (low-dose dex) (n=112), all patients had at least one treatment-emergent adverse reaction.
·       In the POMALYST alone versus POMALYST + low dose dexamethasone arms, respectively, most common adverse reactions (≥30%) included fatigue and asthenia (55%, 63%), neutropenia (52%, 47%), anemia (38%, 39%), constipation (36%, 35%), nausea (36%,22%), diarrhea (34%, 33%), dyspnea (34%, 45%), upper respiratory tract infection (32%, 25%), back pain (32%, 30%), and pyrexia (19%, 30%)
·       90% of patients treated with POMALYST alone and 88% of patients treated with POMALYST + low-dose dex had at least one treatment-emergent NCI CTC Grade 3 or 4 adverse reaction
·       In the POMALYST alone versus POMALYST + low dose dexamethasone arms, respectively, most common Grade 3/4 adverse reactions (≥15%) included neutropenia (47%, 38%), anemia (22%, 21%), thrombocytopenia (22%, 19%), and pneumonia (16%, 23%). For other Grade 3 or 4 toxicities besides neutropenia and thrombocytopenia, hold treatment and restart treatment at 1 mg less than the previous dose when toxicity has resolved to less than or equal to Grade 2 at the physician’s discretion  
·       67% of patients treated with POMALYST and 62% of patients treated with POMALYST + low-dose dex had at least one treatment-emergent serious adverse reaction
·       In the POMALYST alone versus POMALYST + low dose dexamethasone arms, respectively, most common serious adverse reactions (≥5%) were pneumonia (14%, 19%), renal failure (8%, 6%), dyspnea (5%, 6%), sepsis (6%, 3%), pyrexia (3%, 5%) dehydration (5%, 3%), hypercalcemia (5%, 2%),urinary tract infection (0%, 5%), and febrile neutropenia (5%, 1%)

DRUG INTERACTIONS
No formal drug interaction studies have been conducted with POMALYST. Pomalidomide is primarily metabolized by CYP1A2 and CYP3A. Pomalidomide is also a substrate for P-glycoprotein (P-gp). Coadministration of POMALYST with drugs that are strong inhibitors or inducers of CYP1A2, CYP3A, or P-gp should be avoided. Cigarette smoking may reduce pomalidomide exposure due to CYP1A2 induction. Patients should be advised that smoking may reduce the efficacy of pomalidomide.

USE IN SPECIFIC POPULATIONS

Pregnancy: If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling.  Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-332-1088 and also to Celgene Corporation at 1-888-423-5436.

Nursing Mothers: It is not known if pomalidomide is excreted in human milk. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from POMALYST, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: Safety and effectiveness of POMALYST in patients under the age of 18 have not been established.

Geriatric Use: No dosage adjustment is required for POMALYST based on age. Patients greater than or equal to 65 years of age were more likely than patients less than or equal to 65 years of age to experience pneumonia.

Renal and Hepatic Impairment: Pomalidomide is metabolized in the liver. Pomalidomide and its metabolites are primarily excreted by the kidneys. The influence of renal and hepatic impairment on the safety, efficacy, and pharmacokinetics of pomalidomide has not been evaluated. Avoid POMALYST in patients with a serum creatinine >3.0 mg/dL. Avoid POMALYST in patients with serum bilirubin >2.0 mg/dL and AST/ALT >3.0 x ULN.

Please see full Prescribing Information, including Boxed WARNINGS, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.


POMALYST (pomalidomide) is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy.  Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.
  
About Multiple Myeloma
Multiple myeloma (also known as myeloma or plasma cell myeloma) is a cancer of the blood in which malignant plasma cells are overproduced in the bone marrow. Plasma cells are white blood cells that help produce antibodies called immunoglobulins that fight infection and disease. However, most patients with multiple myeloma have cells that produce a form of immunoglobulin called paraprotein (or M protein) that does not benefit the body. In addition, the malignant plasma cells replace normal plasma cells and other white blood cells important to the immune system. Multiple myeloma cells can also attach to other tissues of the body, such as bone, and produce tumors.[1] The cause of the disease remains unknown.[2]

About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of novel therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the company’s Web site at www.celgene.com.


[1]http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma
[2]http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-causes


I Had Fun Today

I had a chance today to address employees of Celgene, makers of pomalidomide, the investigational drug that has kept my myeloma stable for more than four years now.  I’m grateful for the drug, and told them so.  They seemed pleased, and I had a lot of fun.

Celgene recently announced that they have submitted pomalidomide to the FDA for approval, see previous post.  I will be delighted when the drug is accessible to even more people.