According to my research, the best combined treatments for MM are botrezomib and thalidomide. Targeting the proteasome inside myeloma cells looks to be the most efficient way to fight this type of cancer

1. MULTIPLE MYELOMA
Thalidomide and Bortezomib Treatment in Patients with MM
Mohammad Alanazi

2. OVERVIEW (1)
• Multiple myeloma is a bone marrow cancer that caused by abnormal plasma cells.
• Abnormal plasma cells take out the majority of space in the bone marrow.
• Structural bone damage
• Antibodies?
• Multiple?
• M protein, M spike, and MGUS.

3. OVERVIEW
(1) www.cancer.net (1) www.cancer.net

4. SYMPTOMS (2)
• Bone problems (pain, weakness, broken bones)
• Low blood counts (anemia, leukopenia, thrombocytopenia)
• Hypercalcemia (thirst, urination, kidney problems, loss of appetite,
confusion)
• Nervous system symptoms (numbness, muscle weakness)

5. B-CELL ABNORMALITY
(3) www.biographicswed.com (4) www.moderncancerhospital.com

6. CAUSES
• IL-6: inhibits tumor cell apoptosis and triggers proliferation. (5)
• Autocrine and Paracrine. (6)
• Upregulated IL-6 signaling could activate the oncogenic STAT3 pathway. (6)

7. THALIDOMIDE
Immunomodulator
Mechanism of action: (8)
• No precise mechanism of action is
known
• Possible mechanisms are:
- Inhibits TNF-a, IL-6
- Costimulates T-cells, and
modulates NK cells cytotoxicity
(7 )Kumar, S. (2005, May).

8. BORTEZOMIB
• Targeted Chemotherapy
• Slowing or blocking the action of
proteasomes, which are responsible for
degrading proteins inside the normal or
the cancerous cells. The excess protein
inside the cancerous cells may cause
them to stop growing(cell cycle arrest),
dividing, and then causing them to
die(apoptosis). (9,10)
(10) www.velcade.com

9. BORTEZOMIB
(9)www.nature.com

10. SIDE EFFECTS
• Thalidomide: (11)
- Anxiety
- Chest pain
- Cough
- Dizziness or lightheadedness
- Fainting
- Fast heartbeat
- Muscle weakness
- Pain, redness, or swelling in the arm or leg
- Sudden shortness of breath or troubled
breathing
- Tingling, burning, numbness, or pain in the
hands, arms, feet, or legs
• Bortezomib: (12)
- Fatigue
- Peripheral neuropathy
- Low blood pressure
- Heart problems
- Lung problems
- Liver problems
- Nausea
- Low red blood cells level
- Fever
- Decreased appetite

11. CLINICAL TRAIL: BORTEZOMIB AND THALIDOMIDE IN
TREATING PATIENTS WITH NEWLY DIAGNOSED STAGE II OR STAGE
III MULTIPLE MYELOMA. (13)
• NCT00287872
• PURPOSE: studying how well giving bortezomib together with thalidomide works in treating
patients with newly diagnosed stage II or stage III multiple myeloma.
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Baltimore, Maryland,
United States, 21231-2410
• Duration: 2006-2014
• Phase 2
• Study type: Interventional
• 1 Arm: Bortezomib and Thalidomide
• Frequency: patients will receive Bortezomib on days 1, 4, 8, and 11 in each 21 days cycle
with daily oral Thalidomide for at least four courses(1 to 6 months).
• Enrollment: 30 patients, older than 18, newly diagnosed with stage 2 or 3 Multiple Myeloma.

12. RESULTS (13)
Serious adverse events
Response to treatment

13. LONG-TERM OUTCOMES OF DIFFERENT
BORTEZOMIB-BASED REGIMENS IN CHINESE
MYELOMA PATIENTS (14)

14. EFFICACY OF BORTEZOMIB AND THALIDOMIDE (14)
Overall survival: from the time of diagnosis
until death ..
Progression-free survival: the period from the
initiation of chemotherapy to the time of the
first sign or relapse
Bortezomib + Dexamethasone. (PD)
Botrezomib + Liposomal doxorubicin. (PAD)
Bortezomib + Thalidomide. (PTD)

15. CONCLUSION
• Combined treatment has the most effective results on patient with MM. (14)
• The main focus has turned to inhibit the function of the proteasome inside
myeloma cells. (15)
• From my prospective, understanding the main defect(s) behind the occurrence
of Multiple Myeloma is the key to find the suitable treatment for this serious
disease.
• However, MM is a complex disease especially when we consider where the
disease occurs, and the defect begins in early stage of the stem cell maturation.

16. REFERENCES
(1) Cancer.Net, Editor board. Multiple Myeloma. Cancer.net http://www.cancer.net/cancer-types/multiple-
myeloma/overview. Accessed Feb 11 2016
(2) Signs and symptoms of multiple myeloma. (n.d.). Retrieved February 20, 2016, from
http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-signs-symptoms
(3) Medical illustration and design. Biographics. (n.d.). Retrieved February 20, 2016, from
http://www.biographicsweb.com/illustration.htm
(4) Multiple Myeloma | Modern Cancer Hospital Guangzhou, China. (n.d.). Retrieved February 20, 2016,
from http://www.moderncancerhospital.com/cancer/multiple-myeloma/
(5) Urashima, M. (n.d.). Interleukin-6 Promotes Multiple Myeloma Cell Growth Via Phosphorylation of
Retinoblastoma Protein. Retrieved February 20, 2016.
(6) Autocrine signalling. (n.d.). Retrieved February 20, 2016, from
https://en.wikipedia.org/wiki/Autocrine_signalling#IL-6_Autocrine_Signaling

17. REFERENCES
(7) Kumar, S. (2005, May). Drug Insight:Thalidomide as a treatment for multiple myeloma.
(8) Thalidomide. (n.d.). Retrieved February 20, 2016, from https://en.wikipedia.org/wiki/Thalidomide.
(9) Hot Drugs 2004. (n.d.). Retrieved February 20, 2016, from
http://www.nature.com/nrd/journal/v3/n7_supp/full/nrd1406.html
(10) How VELCADE® (bortezomib) works. (n.d.). Retrieved February 20, 2016, from
http://www.velcade.com/Understanding-velcade/About-velcade
(11) Thalidomide Side Effects in Detail - Drugs.com. (n.d.). Retrieved February 20, 2016, from
http://www.drugs.com/sfx/thalidomide-side-effects.html
(12) Bortezomib Side Effects in Detail - Drugs.com. (n.d.). Retrieved February 20, 2016, from
http://www.drugs.com/sfx/bortezomib-side-effects.html
(13) N, G. (n.d.). Bortezomib and Thalidomide in Treating Patients With Newly Diagnosed Stage II or
Stage III Multiple Myeloma. Retrieved February 20, 2016, from
https://clinicaltrials.gov/ct2/show/results/NCT00287872?term=thalidomide and multiple myeloma
(14)Wang, H. (2016, January). Long-term outcomes of different bortezomib-based regimens in Chinese
myeloma patients. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4734823/
(15) Adams, J. "The Proteasome: Structure, Function, and Role in the Cell." Cancer Treatment Reviews 29
(2003): 3-9.Web.